You searched for subject:(Chondrocyte).
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175 total matches.
◁ [1] [2] [3] [4] [5] [6] ▶
Mississippi State University
1.
Mochal-King, Cathleen Ann.
ANTIBIOTICS INDUCE PROSTAGLADIN E2 PRODUCTION AND CYTOTOXICITY IN EQUINE CHONDROCYTES THAT CAN BE INHIBITED BY AVOCADO SOYBEAN UNSAPONIFIABLES, GLUCOSAMINE, AND CHONDROITIN SULFATE.
Degree: MS, Veterinary Medicine, College of, 2011, Mississippi State University
URL: http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042011-170643/ 
;
► Amikacin (AK) and enrofloxacin (EF) concentrations consistent with intra-articular and regional limb perfusion were evaluated for their effects on equine chondrocytes. We evaluated the…
(more)
▼ Amikacin
(AK) and enrofloxacin (EF) concentrations consistent with intra-articular and
regional limb perfusion were evaluated for their effects on equine
chondrocytes. We evaluated the
production of prostaglandin E
2 (PGE
2)
by
equine chondrocytes in response to AK and EF administration,and if the combination of avocado soybean
unsaponifiables (ASU), glucosamine (GLU), and chondroitin sulfate (CS) could
reduce the production of PGE
2. Monolayer cell cultures of equine
chondrocytes were treated with clinically relevant concentrations of AK and EF
plus combinations of ASU, GLU, and CS.AK and EF generated a dose dependent cytotoxicity. The induction of PGE
2 following EF
administration was significantly greater than PGE
2 levels induced by
positive controls. Induction of PGE
2
by EF was significantly reduced in chondrocytes pretreated with ASU, GLU, and
CS. We have demonstrated for the first time that EF can induce production of
PGE
2 in equine chondrocytes and that this effect can be attenuated
with the combination of ASU, GLU, and CS.
Advisors/Committee Members: Robert L. Linford (chair).
Subjects/Keywords: amikacin; enrofloxacin; chondrocyte
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APA (6th Edition):
Mochal-King, C. A. (2011). ANTIBIOTICS INDUCE PROSTAGLADIN E2 PRODUCTION AND CYTOTOXICITY IN EQUINE CHONDROCYTES THAT CAN BE INHIBITED BY AVOCADO SOYBEAN UNSAPONIFIABLES, GLUCOSAMINE, AND CHONDROITIN SULFATE. (Masters Thesis). Mississippi State University. Retrieved from http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042011-170643/ ;
Chicago Manual of Style (16th Edition):
Mochal-King, Cathleen Ann. “ANTIBIOTICS INDUCE PROSTAGLADIN E2 PRODUCTION AND CYTOTOXICITY IN EQUINE CHONDROCYTES THAT CAN BE INHIBITED BY AVOCADO SOYBEAN UNSAPONIFIABLES, GLUCOSAMINE, AND CHONDROITIN SULFATE.” 2011. Masters Thesis, Mississippi State University. Accessed April 13, 2021.
http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042011-170643/ ;.
MLA Handbook (7th Edition):
Mochal-King, Cathleen Ann. “ANTIBIOTICS INDUCE PROSTAGLADIN E2 PRODUCTION AND CYTOTOXICITY IN EQUINE CHONDROCYTES THAT CAN BE INHIBITED BY AVOCADO SOYBEAN UNSAPONIFIABLES, GLUCOSAMINE, AND CHONDROITIN SULFATE.” 2011. Web. 13 Apr 2021.
Vancouver:
Mochal-King CA. ANTIBIOTICS INDUCE PROSTAGLADIN E2 PRODUCTION AND CYTOTOXICITY IN EQUINE CHONDROCYTES THAT CAN BE INHIBITED BY AVOCADO SOYBEAN UNSAPONIFIABLES, GLUCOSAMINE, AND CHONDROITIN SULFATE. [Internet] [Masters thesis]. Mississippi State University; 2011. [cited 2021 Apr 13].
Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042011-170643/ ;.
Council of Science Editors:
Mochal-King CA. ANTIBIOTICS INDUCE PROSTAGLADIN E2 PRODUCTION AND CYTOTOXICITY IN EQUINE CHONDROCYTES THAT CAN BE INHIBITED BY AVOCADO SOYBEAN UNSAPONIFIABLES, GLUCOSAMINE, AND CHONDROITIN SULFATE. [Masters Thesis]. Mississippi State University; 2011. Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-04042011-170643/ ;
University of Manchester
2.
Szkolar, Laura.
The Development of Functional Peptide Scaffolds for Cell
Culture.
Degree: 2016, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:298798
► Peptides and peptide derivatives have shown great scope as biomaterials and for biomedicaltherapy application. It has been demonstrated that classes of these peptides can form…
(more)
▼ Peptides and peptide derivatives have shown great
scope as biomaterials and for biomedicaltherapy application. It has
been demonstrated that classes of these peptides can form fibrillar
hydrogels making them a good candidate for ECM mimics. In
particular, the ionic complementary peptides, composed of
alternating hydrophobic and hydrophilic amino acidshave been
reported as successful cell scaffolds. The simple structure of such
ionic complementary peptides is generally seen to spontaneously
self-assemble into β-sheet richfibrils in the presence of water.
The highly aqueous environment, along with the inter meshing of
fibres, results in an architecture akin to the natural ECM of the
body, making peptide hydrogels highly suitable as cell culture
scaffolds. The structure of such hydrogels, usually comprising 8-32
amino acids, has been widely reported as easily modifiable, thus,
allowing for control of the final material properties.This study
explores the potential use of a range of ionic-complementary
peptides for the culture of primary bovine chondrocytes.
Modifications and additions to peptide sequence, such as charge and
amino acid substitution, were investigated. In all studies only 1
design parameter (sequence, charge etc.) was varied, to allow for
better understanding of the effect of materials properties upon
cell response.The encapsulation of primary bovine chondrocytes was
undertaken, with the aim of providing a suitable cell scaffold
capable of maintaining
chondrocyte viability and function in vitro.
Despite in vivo work being beyond the scope of this thesis, the
properties of the hydrogel scaffold were designed with final aim of
being suitable for use with matrix associated autologous
chondrocyte implantation (MACI) in clinical
therapy.
Advisors/Committee Members: GOUGH, JULIE JE, Gough, Julie, Saiani, Alberto.
Subjects/Keywords: peptide; chondrocyte; hydrogel
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Szkolar, L. (2016). The Development of Functional Peptide Scaffolds for Cell
Culture. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:298798
Chicago Manual of Style (16th Edition):
Szkolar, Laura. “The Development of Functional Peptide Scaffolds for Cell
Culture.” 2016. Doctoral Dissertation, University of Manchester. Accessed April 13, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:298798.
MLA Handbook (7th Edition):
Szkolar, Laura. “The Development of Functional Peptide Scaffolds for Cell
Culture.” 2016. Web. 13 Apr 2021.
Vancouver:
Szkolar L. The Development of Functional Peptide Scaffolds for Cell
Culture. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Apr 13].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:298798.
Council of Science Editors:
Szkolar L. The Development of Functional Peptide Scaffolds for Cell
Culture. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:298798
University of Rochester
3.
Chen, Tony (1981 - ).
The Role of interstitial fluid flow as a mediator of
matrix anisotropy and as a protective mechanism against
inflammation in cartilage tissue engineering.
Degree: PhD, 2011, University of Rochester
URL: http://hdl.handle.net/1802/14143
► Injuries to articular cartilage are debilitating and typically require surgical intervention due to the tissue’s inability to self-repair. Current surgical options for focal cartilage defects…
(more)
▼ Injuries to articular cartilage are debilitating
and typically require surgical intervention due to the tissue’s
inability to self-repair. Current surgical options for focal
cartilage defects are successful only in treating the associated
symptoms, but produce inconsistent clinical outcomes in the long
term, and are implicated in degenerative joint changes years later.
As an alternative, functional tissue engineering may soon offer
translational approaches for cartilage repair by producing
implantable artificial tissues that recapitulate the composition,
structure, and function of the native tissue. While current tissue
engineering bioreactors that introduce various physiologically
inspired mechanical stimuli are able to reproduce the mechanical
properties of native cartilage, recreating the tissue’s structural
and compositional anisotropy, which might influence the integration
of the implanted tissue with the surrounding cartilage, has to date
remained elusive. Furthermore, the fate of the engineered construct
during the inflammatory phase that ensues upon implantation in the
joint has been less studied, as most of the literature focuses on
developing engineered cartilage in idealized culture conditions in
vitro, and for the most part neglects the interplay between
inflammation and repair mechanobiology.
This
dissertation sets to recreate aspects of the characteristic zonal
anisotropy of articular cartilage using custom-designed bioreactors
based on Couette and Poiseuille flow with the hypothesis that
interstitial fluid flow can influence matrix synthesis and the
alignment of collagen fibers. Using in situ hybridization and
immunohistochemistry, tissue engineered cartilage (TEC) hydrogels
that were cultured in a novel bioreactor that simulates rotational
Couette flow demonstrated an increase in aggrecan and type II
collagen mRNA expression and protein synthesis near the surface of
the hydrogel exposed to the flow, compared to deeper regions within
the hydrogel and control hydrogels not stimulated by Couette flow.
Furthermore, the alignment of the collagen fibers in the
superficial layer of the bioreactor-cultured TEC hydrogels was
significantly enhanced compared to controls. When quantified using
Fast Fourier Transform (FFT) algorithms, the collagen alignment in
the surface region of the bioreactor-cultured TEC hydrogels was
remarkably similar to the alignment pattern of collagen in the
superficial zone of native articular cartilage.
To
formally test the hypothesis that the aforementioned effects of
Couette flow are related to interstitial flow fields, the
interstitial flow velocity profiles within TEC hydrogels were
experimentally measured as a function of flow rate through a
parallel plate (Poiseuille flow) bioreactor using a flow
visualization technique based on Fluorescence Recovery After
Photobleaching (FRAP). Experimental measurements of the fluid
velocity profile over a range of flow rates demonstrated that
Poiseuille flow induced measurable interstitial flow fields near
the flow-exposed surface of…
Subjects/Keywords: Collagen alignment; Chondrocyte; TNF-&alpha
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chen, T. (. -. ). (2011). The Role of interstitial fluid flow as a mediator of
matrix anisotropy and as a protective mechanism against
inflammation in cartilage tissue engineering. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/14143
Chicago Manual of Style (16th Edition):
Chen, Tony (1981 - ). “The Role of interstitial fluid flow as a mediator of
matrix anisotropy and as a protective mechanism against
inflammation in cartilage tissue engineering.” 2011. Doctoral Dissertation, University of Rochester. Accessed April 13, 2021.
http://hdl.handle.net/1802/14143.
MLA Handbook (7th Edition):
Chen, Tony (1981 - ). “The Role of interstitial fluid flow as a mediator of
matrix anisotropy and as a protective mechanism against
inflammation in cartilage tissue engineering.” 2011. Web. 13 Apr 2021.
Vancouver:
Chen T(-). The Role of interstitial fluid flow as a mediator of
matrix anisotropy and as a protective mechanism against
inflammation in cartilage tissue engineering. [Internet] [Doctoral dissertation]. University of Rochester; 2011. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1802/14143.
Council of Science Editors:
Chen T(-). The Role of interstitial fluid flow as a mediator of
matrix anisotropy and as a protective mechanism against
inflammation in cartilage tissue engineering. [Doctoral Dissertation]. University of Rochester; 2011. Available from: http://hdl.handle.net/1802/14143
University of Manchester
4.
Szkolar, Laura.
The development of functional peptide scaffolds for cell culture.
Degree: PhD, 2016, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/the-development-of-functional-peptide-scaffolds-for-cell-culture(6e7dffc3-030c-4c9e-873e-8ed1f48efa51).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.728122
► Peptides and peptide derivatives have shown great scope as biomaterials and for biomedicaltherapy application. It has been demonstrated that classes of these peptides can form…
(more)
▼ Peptides and peptide derivatives have shown great scope as biomaterials and for biomedicaltherapy application. It has been demonstrated that classes of these peptides can form fibrillar hydrogels making them a good candidate for ECM mimics. In particular, the ionic complementary peptides, composed of alternating hydrophobic and hydrophilic amino acidshave been reported as successful cell scaffolds. The simple structure of such ionic complementary peptides is generally seen to spontaneously self-assemble into β-sheet richfibrils in the presence of water. The highly aqueous environment, along with the inter meshing of fibres, results in an architecture akin to the natural ECM of the body, making peptide hydrogels highly suitable as cell culture scaffolds. The structure of such hydrogels, usually comprising 8-32 amino acids, has been widely reported as easily modifiable, thus, allowing for control of the final material properties. This study explores the potential use of a range of ionic-complementary peptides for the culture of primary bovine chondrocytes. Modifications and additions to peptide sequence, such as charge and amino acid substitution, were investigated. In all studies only 1 design parameter (sequence, charge etc.) was varied, to allow for better understanding of the effect of materials properties upon cell response. The encapsulation of primary bovine chondrocytes was undertaken, with the aim of providing a suitable cell scaffold capable of maintaining chondrocyte viability and function in vitro. Despite in vivo work being beyond the scope of this thesis, the properties of the hydrogel scaffold were designed with final aim of being suitable for use with matrix associated autologous chondrocyte implantation (MACI) in clinical therapy.
Subjects/Keywords: 610.28; peptide; chondrocyte; hydrogel
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Szkolar, L. (2016). The development of functional peptide scaffolds for cell culture. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/the-development-of-functional-peptide-scaffolds-for-cell-culture(6e7dffc3-030c-4c9e-873e-8ed1f48efa51).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.728122
Chicago Manual of Style (16th Edition):
Szkolar, Laura. “The development of functional peptide scaffolds for cell culture.” 2016. Doctoral Dissertation, University of Manchester. Accessed April 13, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/the-development-of-functional-peptide-scaffolds-for-cell-culture(6e7dffc3-030c-4c9e-873e-8ed1f48efa51).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.728122.
MLA Handbook (7th Edition):
Szkolar, Laura. “The development of functional peptide scaffolds for cell culture.” 2016. Web. 13 Apr 2021.
Vancouver:
Szkolar L. The development of functional peptide scaffolds for cell culture. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2021 Apr 13].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-development-of-functional-peptide-scaffolds-for-cell-culture(6e7dffc3-030c-4c9e-873e-8ed1f48efa51).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.728122.
Council of Science Editors:
Szkolar L. The development of functional peptide scaffolds for cell culture. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-development-of-functional-peptide-scaffolds-for-cell-culture(6e7dffc3-030c-4c9e-873e-8ed1f48efa51).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.728122
University of Manchester
5.
Jones, Rebecca.
The chondroprotective effect of urocortin involves
modulation of the mechanosensitive ion channel Piezo1.
Degree: 2019, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322543
► Osteoarthritis (OA) is one of the leading causes of morbidity worldwide. Single injurious mechanical impact to joints as seen in sports injury is known to…
(more)
▼ Osteoarthritis (OA) is one of the leading causes of
morbidity worldwide. Single injurious mechanical impact to joints
as seen in sports injury is known to be associated with a high risk
of later development of OA, known as post-traumatic OA (PTOA). PTOA
affects a younger population of patients and significantly
increases the socio-economic burden of the disease on society.
Breakdown of articular cartilage in the joint is one of the
characterising features of OA. Cartilage is populated with
chondrocytes responsible for production and turnover of the matrix.
Chondrocyte death is known to occur following impact, suggesting a
chondroprotective agent might provide a promising candidate as a
disease modifying drug. Urocortin (Ucn), a small peptide member of
the Corticotrophin- Releasing Factor (CRF) family, has previously
been seen to be essential for chondrocyte survival, where depletion
of Ucn led to chondrocyte cell death. This thesis sought to
elucidate the mechanism of this chondroprotection by Ucn. Initial
chondrocyte cell line and monolayer primary cell studies showed a
significant increase in calcium influx when cells were deprived of
Ucn. A siRNA screen of candidate ion channels highlighted Piezo1 as
being involved in this excessive influx. An ex-vivo model of single
impact then was developed to study the effect of overloading on
cartilage explants over a short timeframe. Both pre-impact and
crucially post-impact addition of Ucn to porcine explants
significantly increased chondrocyte survival 72 hrs after
challenge. This corresponded to a reduction in excessive calcium
influx. Further study with specific mechanosensitive ion channel
blockers and activators confirmed Piezo1 as the ion channel
modulated by Ucn in order to prevent this calcium overload.
Observation of these cells on a subcellular level highlighted a
distinct programmed cell death response to impact, although
molecular biology techniques indicated this was in the absence of
caspase-3 activation. This work has detailed a previously unseen
chondroprotective role of Ucn in response to single impact. In
particular, the protection observed even when Ucn was added
postimpact suggests Ucn as an interesting candidate for further
study in a post-impact injury context, thereby limiting chondrocyte
cell death early after damage and potentially leading to a reduced
incidence of PTOA.
Four digitial videos on Youtube - links contained
within the text
Advisors/Committee Members: RICHARDSON, STEPHEN SMA, SAYAN, BERNA BS, Townsend, Paul, Richardson, Stephen, Sayan, Berna.
Subjects/Keywords: chondrocyte; cartilage; osteoarthritis; urocortin; piezo1
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jones, R. (2019). The chondroprotective effect of urocortin involves
modulation of the mechanosensitive ion channel Piezo1. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322543
Chicago Manual of Style (16th Edition):
Jones, Rebecca. “The chondroprotective effect of urocortin involves
modulation of the mechanosensitive ion channel Piezo1.” 2019. Doctoral Dissertation, University of Manchester. Accessed April 13, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322543.
MLA Handbook (7th Edition):
Jones, Rebecca. “The chondroprotective effect of urocortin involves
modulation of the mechanosensitive ion channel Piezo1.” 2019. Web. 13 Apr 2021.
Vancouver:
Jones R. The chondroprotective effect of urocortin involves
modulation of the mechanosensitive ion channel Piezo1. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Apr 13].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322543.
Council of Science Editors:
Jones R. The chondroprotective effect of urocortin involves
modulation of the mechanosensitive ion channel Piezo1. [Doctoral Dissertation]. University of Manchester; 2019. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:322543
University of Manchester
6.
Jones, Rebecca.
The chondroprotective effect of urocortin involves modulation of the mechanosensitive ion channel Piezo1.
Degree: PhD, 2019, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/the-chondroprotective-effect-of-urocortin-involves-modulation-of-the-mechanosensitive-ion-channel-piezo1(a3216810-a542-4f27-bbdb-78bbdb86f56a).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.820085
► Osteoarthritis (OA) is one of the leading causes of morbidity worldwide. Single injurious mechanical impact to joints as seen in sports injury is known to…
(more)
▼ Osteoarthritis (OA) is one of the leading causes of morbidity worldwide. Single injurious mechanical impact to joints as seen in sports injury is known to be associated with a high risk of later development of OA, known as post-traumatic OA (PTOA). PTOA affects a younger population of patients and significantly increases the socio-economic burden of the disease on society. Breakdown of articular cartilage in the joint is one of the characterising features of OA. Cartilage is populated with chondrocytes responsible for production and turnover of the matrix. Chondrocyte death is known to occur following impact, suggesting a chondroprotective agent might provide a promising candidate as a disease modifying drug. Urocortin (Ucn), a small peptide member of the Corticotrophin- Releasing Factor (CRF) family, has previously been seen to be essential for chondrocyte survival, where depletion of Ucn led to chondrocyte cell death. This thesis sought to elucidate the mechanism of this chondroprotection by Ucn. Initial chondrocyte cell line and monolayer primary cell studies showed a significant increase in calcium influx when cells were deprived of Ucn. A siRNA screen of candidate ion channels highlighted Piezo1 as being involved in this excessive influx. An ex-vivo model of single impact then was developed to study the effect of overloading on cartilage explants over a short timeframe. Both pre-impact and crucially post-impact addition of Ucn to porcine explants significantly increased chondrocyte survival 72 hrs after challenge. This corresponded to a reduction in excessive calcium influx. Further study with specific mechanosensitive ion channel blockers and activators confirmed Piezo1 as the ion channel modulated by Ucn in order to prevent this calcium overload. Observation of these cells on a subcellular level highlighted a distinct programmed cell death response to impact, although molecular biology techniques indicated this was in the absence of caspase-3 activation. This work has detailed a previously unseen chondroprotective role of Ucn in response to single impact. In particular, the protection observed even when Ucn was added postimpact suggests Ucn as an interesting candidate for further study in a post-impact injury context, thereby limiting chondrocyte cell death early after damage and potentially leading to a reduced incidence of PTOA.
Subjects/Keywords: piezo1; chondrocyte; cartilage; osteoarthritis; urocortin
Record Details
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Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jones, R. (2019). The chondroprotective effect of urocortin involves modulation of the mechanosensitive ion channel Piezo1. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/the-chondroprotective-effect-of-urocortin-involves-modulation-of-the-mechanosensitive-ion-channel-piezo1(a3216810-a542-4f27-bbdb-78bbdb86f56a).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.820085
Chicago Manual of Style (16th Edition):
Jones, Rebecca. “The chondroprotective effect of urocortin involves modulation of the mechanosensitive ion channel Piezo1.” 2019. Doctoral Dissertation, University of Manchester. Accessed April 13, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/the-chondroprotective-effect-of-urocortin-involves-modulation-of-the-mechanosensitive-ion-channel-piezo1(a3216810-a542-4f27-bbdb-78bbdb86f56a).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.820085.
MLA Handbook (7th Edition):
Jones, Rebecca. “The chondroprotective effect of urocortin involves modulation of the mechanosensitive ion channel Piezo1.” 2019. Web. 13 Apr 2021.
Vancouver:
Jones R. The chondroprotective effect of urocortin involves modulation of the mechanosensitive ion channel Piezo1. [Internet] [Doctoral dissertation]. University of Manchester; 2019. [cited 2021 Apr 13].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-chondroprotective-effect-of-urocortin-involves-modulation-of-the-mechanosensitive-ion-channel-piezo1(a3216810-a542-4f27-bbdb-78bbdb86f56a).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.820085.
Council of Science Editors:
Jones R. The chondroprotective effect of urocortin involves modulation of the mechanosensitive ion channel Piezo1. [Doctoral Dissertation]. University of Manchester; 2019. Available from: https://www.research.manchester.ac.uk/portal/en/theses/the-chondroprotective-effect-of-urocortin-involves-modulation-of-the-mechanosensitive-ion-channel-piezo1(a3216810-a542-4f27-bbdb-78bbdb86f56a).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.820085
7.
Guérit, David.
Rôle des miR-29a et miR-574-3p au cours de la différenciation chondrocytaire de la cellule souche mésenchymateuse : Roles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cell.
Degree: Docteur es, Biologie Santé, 2012, Université Montpellier I
URL: http://www.theses.fr/2012MON1T013
► Avec l'augmentation de l'espérance de vie, les pathologies ostéo-articulaires comme l'arthrose ou la polyarthrite rhumatoïde, caractérisées par la dégradation du cartilage articulaire, deviennent de réels…
(more)
▼ Avec l'augmentation de l'espérance de vie, les pathologies ostéo-articulaires comme l'arthrose ou la polyarthrite rhumatoïde, caractérisées par la dégradation du cartilage articulaire, deviennent de réels problèmes de santé publique. Les traitements actuels sont essentiellement symptomatiques et aboutissent en ultime recours à la pose de prothèses. En absence de réparation spontanée du tissu et de traitement efficace, des approches d'ingénierie tissulaire du cartilage sont envisagées. Les techniques actuelles reposent sur la transplantation de chondrocytes autologues mais dans la majorité des cas, cette approche n'apporte pas de résultats supérieurs aux techniques chirurgicales utilisées actuellement. Grâce à leurs propriétés de différenciation, les cellules souches mésenchymateuses (CSM) représentent une nouvelle source de cellules ayant des potentiels thérapeutiques intéressants. Cependant, la complexité du processus de différenciation des CSMs vers des chondrocytes articulaires matures rend difficile l'obtention de cartilage fonctionnel après implantation. Il est donc important de mieux comprendre le processus de différenciation de ces cellules afin de mieux contrôler leur devenir in vivo. C'est pourquoi, le laboratoire s'intéresse au rôle des micro-ARNs (miARNs) dans la régulation du processus de différenciation des CSMs. L'objectif de mon projet de thèse a consisté à identifier des miARNs modulés dans la différenciation chondrocytaire des CSM humaines primaires et à étudier leur rôle et leur régulation au cours de la chondrogenèse. Nous avons identifié deux miARNs : miR-29a dont l'expression diminue progressivement au cours de la différenciation et miR-574-3p dont l'expression augmente rapidement puis est maintenue jusqu'à la fin de la différenciation. Ces deux miARNs sont régulés par le facteur de transcription SOX9 mais de manière opposée : SOX9 inhibe miR-29a et induit miR-574-3p. Nous montrons que SOX9 interagit avec YY1 pour réguler miR-29a mais pas miR-574-3p, ce qui pourrait expliquer les effets opposés de SOX9 sur l'expression des deux miARNs. Nous montrons également que ces miARNs sont des inhibiteurs de la différenciation chondrocytaire et avons identifié FOXO3A et RXRα comme cibles respectives de miR-29a et miR-574-3p. L'inhibition de FOXO3A ou RXRα avant l'induction de la différenciation, en utilisant des siARNs spécifiques ou en sur-exprimant les miARNs correspondants, bloque la différenciation des CSM. Ces résultats confirment sur des CSMs adultes, que ces protéines jouent un rôle important dans la chondrogenèse et que miR-29a et miR-574-3p participent aux processus de régulation de la différenciation chondrocytaire. En conclusion, nous avons identifié deux nouveaux miARNs contrôlés par SOX9 et régulant négativement la chondrogenèse grâce à la modulation de deux gènes cibles, dont l'expression est nécessaire avant d'induire la différenciation chondrocytaire.
Roles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cells. With the constant increase of the…
Advisors/Committee Members: Noël, Danièle (thesis director).
Subjects/Keywords: Arthrose; MicroARN; Chondrocyte; Différenciation; Osteoarthritis; MicroRNA; Chondrocyte; Differentiation
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APA (6th Edition):
Guérit, D. (2012). Rôle des miR-29a et miR-574-3p au cours de la différenciation chondrocytaire de la cellule souche mésenchymateuse : Roles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cell. (Doctoral Dissertation). Université Montpellier I. Retrieved from http://www.theses.fr/2012MON1T013
Chicago Manual of Style (16th Edition):
Guérit, David. “Rôle des miR-29a et miR-574-3p au cours de la différenciation chondrocytaire de la cellule souche mésenchymateuse : Roles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cell.” 2012. Doctoral Dissertation, Université Montpellier I. Accessed April 13, 2021.
http://www.theses.fr/2012MON1T013.
MLA Handbook (7th Edition):
Guérit, David. “Rôle des miR-29a et miR-574-3p au cours de la différenciation chondrocytaire de la cellule souche mésenchymateuse : Roles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cell.” 2012. Web. 13 Apr 2021.
Vancouver:
Guérit D. Rôle des miR-29a et miR-574-3p au cours de la différenciation chondrocytaire de la cellule souche mésenchymateuse : Roles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cell. [Internet] [Doctoral dissertation]. Université Montpellier I; 2012. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2012MON1T013.
Council of Science Editors:
Guérit D. Rôle des miR-29a et miR-574-3p au cours de la différenciation chondrocytaire de la cellule souche mésenchymateuse : Roles of miR-29a and miR-574-3p during the chondrogenic differentiation of mesenchymal stem cell. [Doctoral Dissertation]. Université Montpellier I; 2012. Available from: http://www.theses.fr/2012MON1T013
University of Rochester
8.
Zhang, Yongchun.
B-CATENIN Signaling Integrates with BMP and CCN1
Signaling to Regulate Chondrocyte Differentiation and Cartilage
Development ate.
Degree: PhD, 2015, University of Rochester
URL: http://hdl.handle.net/1802/30113
► This work addresses the central question of how B-CATENIN signaling regulates chondrocyte differentiation during endochondral bone formation and cartilage development through integration with BMP and…
(more)
▼ This work addresses the central question of how
B-CATENIN signaling regulates
chondrocyte differentiation during
endochondral bone formation and cartilage
development through
integration with BMP and CCN1 signaling. Even though the
functions
of B-CATENIN signaling in chondrocytes have been extensively
investigated
through gain-of-function (GOF) and loss-of-function
(LOF) mouse models, the role of
B-CATENIN signaling in the
committed chondrocyte and its downstream effectors are
still
unclear. Here we have discovered that cartilage-derived B-CATENIN
signaling
promotes chondrocyte maturation, angiogenesis, secondary
ossification center (SOC)
formation and bone ossification.
B-CATENIN signaling also induces activation of BMP
signaling and
mediates primary ossification center (POC) formation through BMP
and
TAK1 signaling. Next, we identified a matricellular protein,
CCN1, induced by B-
CATENIN signaling in chondrocytes. In vitro
assays demonstrate that CCN1 is required
and sufficient to drive
chondrocyte maturation. In vivo overexpression of CCN1 in
chondrocytes leads to chondrodysplasia with reduced cell number but
increased cell size,
and results in cartilage degeneration in
adult mice. The increase in the expression of
CCN1 in injured
mouse and human cartilage suggests a correlation between the CCN1
and osteoarthritis progression. Finally, we explored the role of
CCN1 in chondrogenesis
by overexpressing CCN1 in limb mesenchyme.
CCN1 overexpression causes severe
chondrodysplasia and reduction
in the expression of chondrogenic genes indicating a
repressive
role of CCN1 in chondrogenesis. Mice with CCN1 overexpression in
mesenchyme develop multiple joint defects, which eventually results
in cartilage
degradation and bone destruction in the knee joints.
Taken together, these data have
revealed that cartilage-derived
B-CATENIN signaling regulates chondrocyte maturation
and
endochondral bone formation through modulating BMP signaling.
Another novel
finding is that CCN1 signaling induced by B-CATENIN
signaling to promote
chondrocyte maturation but inhibit
chondrogenesis.
Subjects/Keywords: beta-CATENIN; CCN1; BMP2; Chondrocyte; Cartilage
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APA (6th Edition):
Zhang, Y. (2015). B-CATENIN Signaling Integrates with BMP and CCN1
Signaling to Regulate Chondrocyte Differentiation and Cartilage
Development ate. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/30113
Chicago Manual of Style (16th Edition):
Zhang, Yongchun. “B-CATENIN Signaling Integrates with BMP and CCN1
Signaling to Regulate Chondrocyte Differentiation and Cartilage
Development ate.” 2015. Doctoral Dissertation, University of Rochester. Accessed April 13, 2021.
http://hdl.handle.net/1802/30113.
MLA Handbook (7th Edition):
Zhang, Yongchun. “B-CATENIN Signaling Integrates with BMP and CCN1
Signaling to Regulate Chondrocyte Differentiation and Cartilage
Development ate.” 2015. Web. 13 Apr 2021.
Vancouver:
Zhang Y. B-CATENIN Signaling Integrates with BMP and CCN1
Signaling to Regulate Chondrocyte Differentiation and Cartilage
Development ate. [Internet] [Doctoral dissertation]. University of Rochester; 2015. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1802/30113.
Council of Science Editors:
Zhang Y. B-CATENIN Signaling Integrates with BMP and CCN1
Signaling to Regulate Chondrocyte Differentiation and Cartilage
Development ate. [Doctoral Dissertation]. University of Rochester; 2015. Available from: http://hdl.handle.net/1802/30113
Mississippi State University
9.
Dycus, David Lee.
Modulation of inflammation and oxidative stress in canine chondrocytes.
Degree: MS, Veterinary Medicine, College of, 2012, Mississippi State University
URL: http://sun.library.msstate.edu/ETD-db/theses/available/etd-09262012-163241/
;
► Little research has focused on the involvement of oxidative stress as it relates to the pathophysiology of osteoarthritis (OA); while inflammation has been extensively…
(more)
▼ Little research has focused on the involvement of oxidative stress as it relates to
the pathophysiology of osteoarthritis (OA); while inflammation has been extensively
studied. The present study evaluates the ability to modulate the response of canine
chondrocytes to both inflammation and oxidative stress in an <i>in-vitro</i> model.
Chondrocytes were incubated and then stimulated to under-go oxidative stress by using
hydrogen peroxide or inflammation using interleukin-1 beta and tumor necrosis factor
alpha. For inhibition of oxidative stress an antioxidant, N-acetyl-cysteine, was used prior
to induction with hydrogen peroxide in a subset of chondrocytes. Measures of oxidative
stress were superoxide dismutase and reduced glutathione. Prostaglandin E2 was used as
a measurement of inflammation. Chondrocytes responded appropriately to both
oxidative stress and inflammation. The antioxidant N-acetyl-cysteine provided adequate
protection against oxidative stress. Oxidative stress and inflammation should be
considered to play a role in the pathophysiology of canine OA.
Advisors/Committee Members: Carmelita G. Frondoza (committee member), Ron M. McLaughlin (committee member), Jennifer L. Wardlaw (chair).
Subjects/Keywords: canine; chondrocyte; oxidative stress; inflammation; osteoarthritis
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APA (6th Edition):
Dycus, D. L. (2012). Modulation of inflammation and oxidative stress in canine chondrocytes. (Masters Thesis). Mississippi State University. Retrieved from http://sun.library.msstate.edu/ETD-db/theses/available/etd-09262012-163241/ ;
Chicago Manual of Style (16th Edition):
Dycus, David Lee. “Modulation of inflammation and oxidative stress in canine chondrocytes.” 2012. Masters Thesis, Mississippi State University. Accessed April 13, 2021.
http://sun.library.msstate.edu/ETD-db/theses/available/etd-09262012-163241/ ;.
MLA Handbook (7th Edition):
Dycus, David Lee. “Modulation of inflammation and oxidative stress in canine chondrocytes.” 2012. Web. 13 Apr 2021.
Vancouver:
Dycus DL. Modulation of inflammation and oxidative stress in canine chondrocytes. [Internet] [Masters thesis]. Mississippi State University; 2012. [cited 2021 Apr 13].
Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-09262012-163241/ ;.
Council of Science Editors:
Dycus DL. Modulation of inflammation and oxidative stress in canine chondrocytes. [Masters Thesis]. Mississippi State University; 2012. Available from: http://sun.library.msstate.edu/ETD-db/theses/available/etd-09262012-163241/ ;
University of Manchester
10.
Soul, Jamie.
A Systems Biology Approach To Knee
Osteoarthritis.
Degree: 2017, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308443
► A hallmark of the joint disease osteoarthritis (OA) is the degradation of the articularcartilage in the affected joint, debilitating pain and decreased mobility. At present…
(more)
▼ A hallmark of the joint disease osteoarthritis (OA)
is the degradation of the articularcartilage in the affected joint,
debilitating pain and decreased mobility. At present thereare no
disease modifying drugs for treatment of osteoarthritis. This
represents asignificant, unmet medical need as there is a large and
increasing prevalence of OA.Using a systems biology approach, we
aimed to better understand the pathogenicmechanisms of OA and
ultimately aid development of therapeutics.This thesis focuses on
the analysis of gene expression data from human OA
cartilageobtained at total knee replacement (TKR). This
transcriptomics approach gives agenome-wide overview of changes,
but can be challenging to interpret. Network-basedalgorithms
provide a framework for the fusion of knowledge so allowing
effectiveinterpretation. The PhenomeExpress algorithm was developed
as part of this thesis toaid the interpretation of gene expression
data. PhenomeExpress uses known diseasegene associations to
identify relevant dysregulated pathways in the data.PhenomeExpress
was further developed into an ‘app’ for Cytoscape, the widely
usednetwork analysis and visualisation platform.To investigate the
processes that occur during the degradation of cartilage we
examinedthe gene expression of damaged and intact OA cartilage
using RNA-Seq and identifiedkey altered pathways with
PhenomeExpress. A regulatory network driven by fourtranscription
factors accounts for a significant proportion of the observed
differentialexpression of damage-associated genes in the
PhenomeExpress identified pathways. Wefurther explored the role of
the cytokines IL-1 and TNF that have been reported to βdrive the
progression of OA. Comparison of the expression response of in
vitrocytokine-treated explants with the in vivo damage response
revealed major differences,providing little evidence for any
significant role of IL-1 and TNF as drivers of OA βdamage in
vivo.Finally, we examined the heterogeneity of OA through analysis
of cartilage expressionprofiles at TKR. Through a network-based
clustering method, we found two subgroupsof patients on the basis
of their gene expression profiles. These subgroups were found
tohave distinct OA expression perturbations and we identified TGF
and S100A8/9 βsignalling as potentially explaining the observed
differential expression. We developeda RT-qPCR based classifier
that allowed classification of new samples into thesesubgroups so
allowing future assessment of the clinical significance of these
subgroups.The work presented in this thesis includes a novel,
widely-accessible tool for theanalysis of disease gene expression
data, which we used to give new insights into thepathogenesis of
osteoarthritis. We have produced a rich dataset for future research
andour analysis of this data has increased our understanding of
cartilage damage processesand the heterogeneity of
OA.
Supplementary Tables are provided as detailed in
the Appendix.
Advisors/Committee Members: BOOT-HANDFORD, RAYMOND RP, Boot-Handford, Raymond, Schwartz, Jean-Marc.
Subjects/Keywords: Osteoarthritis; Cartilage; Chondrocyte; Bioinformatics; Transcriptomics; Network biology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Soul, J. (2017). A Systems Biology Approach To Knee
Osteoarthritis. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308443
Chicago Manual of Style (16th Edition):
Soul, Jamie. “A Systems Biology Approach To Knee
Osteoarthritis.” 2017. Doctoral Dissertation, University of Manchester. Accessed April 13, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308443.
MLA Handbook (7th Edition):
Soul, Jamie. “A Systems Biology Approach To Knee
Osteoarthritis.” 2017. Web. 13 Apr 2021.
Vancouver:
Soul J. A Systems Biology Approach To Knee
Osteoarthritis. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Apr 13].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308443.
Council of Science Editors:
Soul J. A Systems Biology Approach To Knee
Osteoarthritis. [Doctoral Dissertation]. University of Manchester; 2017. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308443
Vanderbilt University
11.
Wang, Weiguang.
Function of Atf4 in Endochondral Bone Formation.
Degree: PhD, Pharmacology, 2011, Vanderbilt University
URL: http://hdl.handle.net/1803/12726
► Activating transcription factor 4 (Atf4) is a leucine zip transcription factor. Atf4 mutant (Atf4-/-) mice show severe low bone mass and short stature phenotype. Atf4…
(more)
▼ Activating transcription factor 4 (Atf4) is a leucine zip transcription factor. Atf4 mutant (Atf4-/-) mice show severe low bone mass and short stature phenotype. Atf4 is expressed in growth plate chondrocytes. Atf4-/- growth plate shows disturbed and shortened proliferative
chondrocyte zone, expanded hypertrophic zone and decreased expression of Indian hedgehog (Ihh). Atf4 directly binds to the Ihh promoter and activates its transcription. Reactivation of Hh signaling pharmacologically in mouse limb explants corrects the Atf4-/-
chondrocyte proliferation and short limb phenotypes.
Chondrocyte-specific overexpression of Atf4 in Atf4-/- mice restores Ihh expression and Hh signaling, and completely rescues the cartilage defects presented in Atf4-/- embryos. These data demonstrate a
chondrocyte-autonomous function of Atf4 in chondrogenesis. Unexpectedly, Atf4 overexpression in chondrocytes of Atf4-/-;Col2α1-Atf4 mice also rescues the Osteocalcin expression and bone formation normalize in Atf4-/- mice. The differentiation of Atf4-/- osteoblasts induced by the conditioned medium of Atf4-/-;Col2a1-Atf4 cartilage can be blocked by a neutralizing Ihh antibody, indicating that Atf4 in chondrocytes indirectly regulates osteoblast differentiation via Ihh. My study thus identifies a novel autonomous function of Atf4 in chondrocytes for regulating both chondrogenesis and osteogenesis in endochondral ossification.
Advisors/Committee Members: Xiangli Yang (committee member), Chin Chiang (committee member), Charles C Hong (committee member), Douglas P Mortlock (committee member), Florent Elefteriou (committee member).
Subjects/Keywords: chondrocyte; Ihh; Endochondral ossification; Atf4; osteoblast
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APA (6th Edition):
Wang, W. (2011). Function of Atf4 in Endochondral Bone Formation. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12726
Chicago Manual of Style (16th Edition):
Wang, Weiguang. “Function of Atf4 in Endochondral Bone Formation.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed April 13, 2021.
http://hdl.handle.net/1803/12726.
MLA Handbook (7th Edition):
Wang, Weiguang. “Function of Atf4 in Endochondral Bone Formation.” 2011. Web. 13 Apr 2021.
Vancouver:
Wang W. Function of Atf4 in Endochondral Bone Formation. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1803/12726.
Council of Science Editors:
Wang W. Function of Atf4 in Endochondral Bone Formation. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/12726
12.
山下, 美智子.
Uhrf1は軟骨細胞分化を制御し正常な骨格形成に必須である.
Degree: 博士(医学), 2018, Ehime University / 愛媛大学
URL: http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/5401
Subjects/Keywords: Uhrf1; chondrocyte; differentiation
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APA (6th Edition):
山下, . (2018). Uhrf1は軟骨細胞分化を制御し正常な骨格形成に必須である. (Thesis). Ehime University / 愛媛大学. Retrieved from http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/5401
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
山下, 美智子. “Uhrf1は軟骨細胞分化を制御し正常な骨格形成に必須である.” 2018. Thesis, Ehime University / 愛媛大学. Accessed April 13, 2021.
http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/5401.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
山下, 美智子. “Uhrf1は軟骨細胞分化を制御し正常な骨格形成に必須である.” 2018. Web. 13 Apr 2021.
Vancouver:
山下 . Uhrf1は軟骨細胞分化を制御し正常な骨格形成に必須である. [Internet] [Thesis]. Ehime University / 愛媛大学; 2018. [cited 2021 Apr 13].
Available from: http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/5401.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
山下 . Uhrf1は軟骨細胞分化を制御し正常な骨格形成に必須である. [Thesis]. Ehime University / 愛媛大学; 2018. Available from: http://iyokan.lib.ehime-u.ac.jp/dspace/handle/iyokan/5401
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Boston University
13.
Blank, Kevin.
The effect of phosphate availability on chondrocyte metabolism.
Degree: MS, Medical Sciences, 2016, Boston University
URL: http://hdl.handle.net/2144/16797
► Dietary phosphate is essential for normal fracture healing and bone growth. Previous studies have established that mice given a phosphate deficient diet after a fracture…
(more)
▼ Dietary phosphate is essential for normal fracture healing and bone growth. Previous studies have established that mice given a phosphate deficient diet after a fracture demonstrate delayed cartilage maturation and callus mineralization, as well as changes in gene expression consistent with oxidative phosphorylation dysfunction. This study was undertaken in order to examine the role of inorganic and organic phosphate availability on chondrocyte differentiation and mineralization, and to define the relationship between these processes and changes in chondrocyte metabolic function.
ATDC5 murine chondroprogenitor cell line, which has been shown to undergo in vitro differentiation and extracellular matrix mineralization, was cultured under both differentiating and non-differentiating media conditions under conditions in 1mM -0.25mM sodium phosphate monobasic (inorganic phosphate) in the presence or absence of 4mM β-glycerol phosphate (organic phosphate). In the first series of studies, overall cell growth (total DNA and protein contents), mineralization (calcium accumulation), and cell-normalized oxidative metabolism (basal respiration, maximal respiration, ATP turnover, spare capacity, proton leak, and non-mitochondrial respiration rates) were measured over a 28 day time course in cultures grown in differentiating (ascorbic acid, insulin-transferrin-selenium, and β-glycerol phosphate) conditions in 1mM phosphate.
These studies found that when the cells were induced to differentiate, there was a measurable increase in protein content while DNA content decreased by 30%, indicating a fraction of the cells underwent cell death. Differentiation was further associated with an overall two-fold increase in oxidative respiration. Next we assessed how differentiation, the promotion of matrix mineralization, and inorganic phosphate availability affected oxidative respiration. When differentiation was not induced with ascorbic acid and β-glycerol phosphate, there was no over growth in the cultures nor any change in total extracellular matrix mineralization or oxidative respiration. In the absence only of β-glycerol phosphate, differentiation proceeded but matrix mineralization did not occur. However, overall protein content and oxidative respiration were statistically two- and 1.5-fold higher, respectively, independent of the inorganic phosphate contents of the growth media. These results suggest that both differentiation and overall protein accumulation are strongly associated with increased oxidative metabolism while mineralization of the matrix decreased oxidative function. Only at the lowest phosphate levels were changes in basal oxidative function observed. These results are consistent with previous in vivo findings suggesting that diminished expression of mitochondrial associated genes in callus tissues from hypophosphatemic mice were associated with an overall decrease in chondrocyte differentiation.
Subjects/Keywords: Biochemistry; Chondrocyte; Differentiation; Metabolism; Oxidative phosphorylation; Phosphate
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APA (6th Edition):
Blank, K. (2016). The effect of phosphate availability on chondrocyte metabolism. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/16797
Chicago Manual of Style (16th Edition):
Blank, Kevin. “The effect of phosphate availability on chondrocyte metabolism.” 2016. Masters Thesis, Boston University. Accessed April 13, 2021.
http://hdl.handle.net/2144/16797.
MLA Handbook (7th Edition):
Blank, Kevin. “The effect of phosphate availability on chondrocyte metabolism.” 2016. Web. 13 Apr 2021.
Vancouver:
Blank K. The effect of phosphate availability on chondrocyte metabolism. [Internet] [Masters thesis]. Boston University; 2016. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/2144/16797.
Council of Science Editors:
Blank K. The effect of phosphate availability on chondrocyte metabolism. [Masters Thesis]. Boston University; 2016. Available from: http://hdl.handle.net/2144/16797
University of Toronto
14.
Parreno, Justin.
The Role of Cytoskeletal Polymerization in the Regulation of the Chondrocyte Phenotype.
Degree: PhD, 2015, University of Toronto
URL: http://hdl.handle.net/1807/80370
► In this study the role of the chondrocyte cytoskeleton in regulating cellular mRNA levels in chondrocytes was examined. Passaging of chondrocytes in traditional 2D monolayer…
(more)
▼ In this study the role of the chondrocyte cytoskeleton in regulating cellular mRNA levels in chondrocytes was examined. Passaging of chondrocytes in traditional 2D monolayer culture results in chondrocyte dedifferentiation. As compared to primary chondrocytes, passaged cells exhibited a lower g-/f-actin ratio. However tubulin polymerization was not significantly altered by passaging. Pharmacological actin depolymerization partially redifferentiated passaged chondrocytes whereas modulation of tubulin did not.
To delineate the mechanism by which actin polymerization regulates gene expression, myocardin related transcription factor A (MRTF) signaling was investigated. Passaging resulted in an increased amount of MRTFa as well as a predominantly nuclear localization of MRTF; these changes occurred within 5 days of culture and were sustained in passaged chondrocytes. Plating passaged cells in high density 3D or in suspension on top of agarose or exposure of cells in monolayer culture to latrunculin B resulted in increased g-/f-actin, cytoplasmic localization of MRTFa, and fibroblast matrix (col1 and tnc) mRNA levels. Exposure of chondrocytes to MRTFa inhibitor (CCG1423) resulted in only small changed to cell shape did not significantly affect gene expression but did result in reduced fibroblast matrix gene expression.
siRNA mediated MRTF knockdown mimicked some but not all effects on gene expression as actin depolymerization. In addition SRF knockdown did not completely mimic MRTF knockdown. This demonstrated that actin could utilize several different signaling mechanisms to regulate gene expression. Although actin depolymerization did not completely redifferentiate passaged chondrocytes, it appears to be a potent regulator passaged chondrocytes gene expression and initiates the redifferentiation process.
2017-11-30 00:00:00
Advisors/Committee Members: Kandel, Rita A, Laboratory Medicine and Pathobiology.
Subjects/Keywords: Actin; Bioengineering; Cartilage; Chondrocyte; Dedifferentiation; MRTF; 0379
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APA (6th Edition):
Parreno, J. (2015). The Role of Cytoskeletal Polymerization in the Regulation of the Chondrocyte Phenotype. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/80370
Chicago Manual of Style (16th Edition):
Parreno, Justin. “The Role of Cytoskeletal Polymerization in the Regulation of the Chondrocyte Phenotype.” 2015. Doctoral Dissertation, University of Toronto. Accessed April 13, 2021.
http://hdl.handle.net/1807/80370.
MLA Handbook (7th Edition):
Parreno, Justin. “The Role of Cytoskeletal Polymerization in the Regulation of the Chondrocyte Phenotype.” 2015. Web. 13 Apr 2021.
Vancouver:
Parreno J. The Role of Cytoskeletal Polymerization in the Regulation of the Chondrocyte Phenotype. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1807/80370.
Council of Science Editors:
Parreno J. The Role of Cytoskeletal Polymerization in the Regulation of the Chondrocyte Phenotype. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/80370
University of Toronto
15.
Aiken, Alison.
The Fundamental Roles of the Tissue Inhibitor of Metalloproteinase Family in Mammalian Biology.
Degree: PhD, 2014, University of Toronto
URL: http://hdl.handle.net/1807/74489
► The metalloproteinases are a family of extracellular proteases responsible for degrading components of the extracellular matrix as well as shedding growth factors, cytokines and their…
(more)
▼ The metalloproteinases are a family of extracellular proteases responsible for degrading components of the extracellular matrix as well as shedding growth factors, cytokines and their receptors from cell surfaces, impacting signaling, tissue remodeling and homeostasis. The four mammalian tissue inhibitors of metalloproteinases (TIMP1-4) regulate metalloproteinase activity in the tissues. While the TIMPs exhibit some target specificity, functional redundancy exists due to overlapping expression patterns and shared proteinase targets. It is known that the TIMP-metalloproteinase network influences a vast spectrum of biological process and is implicated in most human diseases. Despite this, the fundamental roles of the TIMP family in mammalian development remained unidentified. This thesis describes the generation and characterization of quadruple knockout TIMPless mice deficient for
2016-11-16 00:00:00
Advisors/Committee Members: Khokha, Rama, Medical Biophysics.
Subjects/Keywords: chondrocyte; CXCL12; IHH; metalloproteinase; skeleton; TIMP; 0307
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APA (6th Edition):
Aiken, A. (2014). The Fundamental Roles of the Tissue Inhibitor of Metalloproteinase Family in Mammalian Biology. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/74489
Chicago Manual of Style (16th Edition):
Aiken, Alison. “The Fundamental Roles of the Tissue Inhibitor of Metalloproteinase Family in Mammalian Biology.” 2014. Doctoral Dissertation, University of Toronto. Accessed April 13, 2021.
http://hdl.handle.net/1807/74489.
MLA Handbook (7th Edition):
Aiken, Alison. “The Fundamental Roles of the Tissue Inhibitor of Metalloproteinase Family in Mammalian Biology.” 2014. Web. 13 Apr 2021.
Vancouver:
Aiken A. The Fundamental Roles of the Tissue Inhibitor of Metalloproteinase Family in Mammalian Biology. [Internet] [Doctoral dissertation]. University of Toronto; 2014. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1807/74489.
Council of Science Editors:
Aiken A. The Fundamental Roles of the Tissue Inhibitor of Metalloproteinase Family in Mammalian Biology. [Doctoral Dissertation]. University of Toronto; 2014. Available from: http://hdl.handle.net/1807/74489
University of Melbourne
16.
Falahati, Behzad.
Development of an experimental loading and imaging protocol for studying cartilage cell morphology in a mouse model.
Degree: 2012, University of Melbourne
URL: http://hdl.handle.net/11343/38006
► A methodology was developed to apply controlled cyclic loads on mouse knees and to investigate resulting changes in chondrocyte morphology in vitro using confocal microscopy.…
(more)
▼ A methodology was developed to apply controlled cyclic loads on mouse knees and to investigate resulting changes in chondrocyte morphology in vitro using confocal microscopy. For this purpose, an existing loading device was modified. The legs of wild-type and ADAMTS5-deficient mice were immobilised, and simulated knee joint loading was performed using the loading device. Chondrocytes of the loaded and unloaded knee cartilage samples were subsequently imaged with confocal microscopy, and the volume and sphericity of the chondrocytes, the distance between the chondrocytes, and cell viability were measured.
The experimental results showed that changes in chondrocyte viability and morphology were different in the ADAMTS5-deficient mice compared to the wild-type mice after applying 10 N cyclic loading for one hour. The distance between cells was significantly less in the ADAMTS5-deficient cartilage compared to the wild-type. This suggests that deletion of the ADAMTS5 gene in mice may result in the formation of chondrocyte clusters. However, the chondrocyte clusters may not have adverse effects on the resilience of the cartilage tissue, as chondrocyte viability did not decrease in the ADAMTS5-deficient cartilage after loading. Changes in sphericity and distance between chondrocytes were not statistically significant after loading; however, these results must be interpreted with caution due to the small sample size used in the present study. Assessment of changes in cartilage stiffness in the ADAMTS5-deficient mice may explain the differences observed between chondrocyte viability in the loaded ADAMTS5-deficient and wild-type mouse cartilage samples. Such assessments are suggested for future work.
The loading apparatus and methods developed in this study may also be applied to characterize microstructural changes in subchondral bone, which is believed to play an important role in the etiology of osteoarthritis.
Subjects/Keywords: chondrocyte; mouse; ADAMTS5 gene; loading; confocal microscopy
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APA (6th Edition):
Falahati, B. (2012). Development of an experimental loading and imaging protocol for studying cartilage cell morphology in a mouse model. (Masters Thesis). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38006
Chicago Manual of Style (16th Edition):
Falahati, Behzad. “Development of an experimental loading and imaging protocol for studying cartilage cell morphology in a mouse model.” 2012. Masters Thesis, University of Melbourne. Accessed April 13, 2021.
http://hdl.handle.net/11343/38006.
MLA Handbook (7th Edition):
Falahati, Behzad. “Development of an experimental loading and imaging protocol for studying cartilage cell morphology in a mouse model.” 2012. Web. 13 Apr 2021.
Vancouver:
Falahati B. Development of an experimental loading and imaging protocol for studying cartilage cell morphology in a mouse model. [Internet] [Masters thesis]. University of Melbourne; 2012. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/11343/38006.
Council of Science Editors:
Falahati B. Development of an experimental loading and imaging protocol for studying cartilage cell morphology in a mouse model. [Masters Thesis]. University of Melbourne; 2012. Available from: http://hdl.handle.net/11343/38006
University of Edinburgh
17.
Mohamad Yusof, Loqman.
Longitudinal growth of mammalian bones : a possible role for membrane transporters in mediating chondrocyte hypertrophy.
Degree: PhD, 2012, University of Edinburgh
URL: http://hdl.handle.net/1842/6481
► Long bone lengthening occurs at the growth plate (GP) by well-regulated chondrocyte proliferation, hypertrophy and terminal matrix deposition. GP chondrocyte (GPC) hypertrophy has been implicated…
(more)
▼ Long bone lengthening occurs at the growth plate (GP) by well-regulated chondrocyte proliferation, hypertrophy and terminal matrix deposition. GP chondrocyte (GPC) hypertrophy has been implicated to be the main determinant of bone growth rate; however the mechanism is poorly understood. The work of this thesis examined some of the cellular process that drives the chondrocyte swelling or hypertrophy particularly in a mammalian post natal GPs using living in situ GPC and fixed GP tissues. Confocal scanning microscopy (CLSM) was used to determine living in situ GPC volume and dimension changes in proliferative zone (PZ) through to hypertrophic zone (HZ) chondrocytes of different GPs of various bones. While PZ cells showed similar volumes and dimensions, HZ cells varied in different GPs, even within the same long bone but at opposite ends. However, the hypertrophic cell volume measured at a single post natal age (day 7) was independent of the corresponding bone length. This could reflect a complex interplay between local and systemic factors in different GPs, which occurs throughout the active phase of bone growth. Maintaining GPC morphology was critical in studying GPC hypertrophy using fixed tissues. This work highlighted a problem caused by conventional fixative solutions, which caused up to 44% hypertrophic GPC shrinkage following GP fixation. This artifact appeared to be associated with the hyperosmotic nature of the fixatives used and could be abolished by adjusting the fixative osmolarity close to physiological level (280 mOsm), or could be significantly reduced by bisecting bone tissues prior to tissue fixation. This thesis proposed roles for plasma membrane transporter(s) in mediating GPC hypertrophy. This hypothesis was tested by examining roles of sodium-hydrogen exchanger (NHE) and anion exchanger (AE) in GPC hypertrophy using an ex vivo bone growth inhibition model. Inhibition of bone growth by inhibitors of NHE (EIPA) and AE (DIDS) respectively was shown to be dose-dependent. The histology of bones demonstrated that the late HZ width was significantly reduced in GPs treated with EIPA or DIDS. Although in situ GPC volumes in the PZ and HZ were not notably different in DIDS-treated GP, the cell volumes in both zones were significantly reduced by EIPA treatment. Fluorescence immunohistochemistry revealed distinctive cellular localisations of NHE1 and AE2 in the PZ and early HZ. These results suggest a possible role of AE in mediating GPC volume increase in PZ chondrocytes and those in the early stages of cell hypertrophy, whereas NHE could possibly maintain intracellular pH of GPC throughout all GP zones. This thesis has characterized various changes in volume and dimensions of living in situ GPC from PZ through to HZ of different GPs of postnatal rats. This work emphasized the importance of fixative osmolarity in order to accurately preserve the normal volume/morphology of cells within tissues. Most importantly, this thesis confirmed a potential role of the plasma membrane transporters, AE and NHE in GPC…
Subjects/Keywords: 612; longitudinal growth; membrane transporter; chondrocyte hypertrophy
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APA ·
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APA (6th Edition):
Mohamad Yusof, L. (2012). Longitudinal growth of mammalian bones : a possible role for membrane transporters in mediating chondrocyte hypertrophy. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/6481
Chicago Manual of Style (16th Edition):
Mohamad Yusof, Loqman. “Longitudinal growth of mammalian bones : a possible role for membrane transporters in mediating chondrocyte hypertrophy.” 2012. Doctoral Dissertation, University of Edinburgh. Accessed April 13, 2021.
http://hdl.handle.net/1842/6481.
MLA Handbook (7th Edition):
Mohamad Yusof, Loqman. “Longitudinal growth of mammalian bones : a possible role for membrane transporters in mediating chondrocyte hypertrophy.” 2012. Web. 13 Apr 2021.
Vancouver:
Mohamad Yusof L. Longitudinal growth of mammalian bones : a possible role for membrane transporters in mediating chondrocyte hypertrophy. [Internet] [Doctoral dissertation]. University of Edinburgh; 2012. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1842/6481.
Council of Science Editors:
Mohamad Yusof L. Longitudinal growth of mammalian bones : a possible role for membrane transporters in mediating chondrocyte hypertrophy. [Doctoral Dissertation]. University of Edinburgh; 2012. Available from: http://hdl.handle.net/1842/6481
Freie Universität Berlin
18.
König, Josephine.
Effekte von Polystyrol- und Polyetherimid-Zellkulturinserts mit verschiedenen Rauigkeitsstufen auf die Morphologie, die metabolische Aktivität und das Expressionsprofil artikulärer Chondrozyten.
Degree: 2020, Freie Universität Berlin
URL: http://dx.doi.org/10.17169/refubium-27583
► Autologe Chondrozyten können in vitro kultiviert werden und zur Defektdeckung von Knorpelschäden implantiert werden. Dafür muss eine kleine Menge an autologen Knorpelzellen während einer Biopsie…
(more)
▼ Autologe Chondrozyten können in vitro kultiviert werden und zur Defektdeckung von Knorpelschäden implantiert werden. Dafür muss eine kleine Menge an autologen Knorpelzellen während einer Biopsie aus dem Gelenk entnommen werden und in einer Monolayerkultur expandiert werden. Kommerziell erhältliche Zellkulturplatten rufen dabei eine Dedifferenzierung der Chondrozyten hervor. Aus diesem Grund steigt die Nachfrage nach optimierten Kunststoffen und Oberflächenbeschaffenheiten, die die Proliferation differenzierter Chondrozyten induzieren könnte.
In der vorliegenden Arbeit wurde der Effekt von maßangefertigten Inserts für Multiwell-Platten aus Polystyrol (PS) und Polyetherimid (PEI) mit drei verschieden rauen Oberflächen (R0, RI, RII) auf die Morphologie, die metabolische Aktivität und das Genexpressionsprofil artikulärer Chondrozyten untersucht. Als Kontrolle dienten kommerziell erhältliche Zellkulturplatten. In die Inserts aus PS und PEI mit den drei Rauigkeitsstufen wurden primäre artikuläre Chondrozyten von Hausschweinen ausgesät. Die Zellmorphologie wurde nach 48 Stunden lichtmikroskopisch untersucht. Die metabolische Aktivität der Chondrozyten wurde über eine Zeitspanne von 24 Stunden durch Anwendung des Alamar Blue-Tests bestimmt. Das Genexpressionsprofil der Chondrozyten (Aggrekan, Kollagen Typ I und Kollagen Typ II) wurde mithilfe der Echtzeit-Polymerase-Kettenreaktion (Real Time Detection [RTD]-PCR) analysiert.
Die Chondrozyten, die auf den Zellkulturoberflächen aus PS und PEI kultiviert wurden, bildeten, im Gegensatz zu den Zellen auf der Kontrolloberfläche, nach 24 und 48 Stunden Zellcluster. Diese Beobachtung könnte auf die fehlende Funktionalisierung der zu testenden Inserts zurückgeführt werden, durch die die Anheftung von Zellen erschwert wird. Die metabolische Aktivität der Chondrozyten, die auf PS kultiviert wurden, war im Mittel niedriger als die Aktivität derjenigen, die auf PEI kultiviert wurden. In beiden Fällen war die metabolische Aktivität der Chondrozyten jedoch signifikant geringer als bei Anzucht der Chondrozyten auf kommerziell erhältlichen Zellkulturoberflächen. Im Vergleich zur Kontrolle war die Genexpression des knorpelspezifischen Aggrekans der auf glattem PS und PEI kultivierten Chondrozyten signifikant höher als die derjenigen, die auf der Kontrolloberfläche kultiviert wurden. Die Genexpression beider Kollagen-Typen war dagegen bei beiden Materialien auf glatter und rauer Oberfläche verglichen mit der Kontrolle signifikant geringer.
Insgesamt scheint PEI ein biokompatibles Material für die Zellkultur von Chondrozyten zu sein. Eine zusätzliche chemische Funktionalisierung könnte zukünftig spezifische Oberflächen-Interaktionen oder kovalente Bindungen von stimulatorischen Biomolekülen ermöglichen.
Advisors/Committee Members: female (gender), N.N. (firstReferee), N.N. (furtherReferee).
Subjects/Keywords: cell culture inserts; chondrocyte; ddc:610
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APA (6th Edition):
König, J. (2020). Effekte von Polystyrol- und Polyetherimid-Zellkulturinserts mit verschiedenen Rauigkeitsstufen auf die Morphologie, die metabolische Aktivität und das Expressionsprofil artikulärer Chondrozyten. (Thesis). Freie Universität Berlin. Retrieved from http://dx.doi.org/10.17169/refubium-27583
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
König, Josephine. “Effekte von Polystyrol- und Polyetherimid-Zellkulturinserts mit verschiedenen Rauigkeitsstufen auf die Morphologie, die metabolische Aktivität und das Expressionsprofil artikulärer Chondrozyten.” 2020. Thesis, Freie Universität Berlin. Accessed April 13, 2021.
http://dx.doi.org/10.17169/refubium-27583.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
König, Josephine. “Effekte von Polystyrol- und Polyetherimid-Zellkulturinserts mit verschiedenen Rauigkeitsstufen auf die Morphologie, die metabolische Aktivität und das Expressionsprofil artikulärer Chondrozyten.” 2020. Web. 13 Apr 2021.
Vancouver:
König J. Effekte von Polystyrol- und Polyetherimid-Zellkulturinserts mit verschiedenen Rauigkeitsstufen auf die Morphologie, die metabolische Aktivität und das Expressionsprofil artikulärer Chondrozyten. [Internet] [Thesis]. Freie Universität Berlin; 2020. [cited 2021 Apr 13].
Available from: http://dx.doi.org/10.17169/refubium-27583.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
König J. Effekte von Polystyrol- und Polyetherimid-Zellkulturinserts mit verschiedenen Rauigkeitsstufen auf die Morphologie, die metabolische Aktivität und das Expressionsprofil artikulärer Chondrozyten. [Thesis]. Freie Universität Berlin; 2020. Available from: http://dx.doi.org/10.17169/refubium-27583
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Oklahoma State University
19.
Hooshmand-yazdi, Shirin.
Genistein Reduces Production of Proinflammatory Molecules in Human Chondrocytes.
Degree: Department of Nutritional Sciences, 2006, Oklahoma State University
URL: http://hdl.handle.net/11244/9233
► Previously, we reported that cartilage is an estrogen receptor (ER) positive tissue and that mRNA levels of ER increase in postmenopausal women with osteoarthritis. Based…
(more)
▼ Previously, we reported that cartilage is an estrogen receptor (ER) positive tissue and that mRNA levels of ER increase in postmenopausal women with osteoarthritis. Based on our findings and those of other investigators, we hypothesized that local rather than circulating estrogen levels negatively affect
chondrocyte metabolism and that selective estrogen receptor modulators (SERM) augment cartilage health. To test the latter part of our hypothesis, we explored the role of genistein, a naturally occurring SERM with high affinity to bind ER, in inhibiting the lipopolysaccharide (LPS)-stimulated cyclooxygenase (COX)-2 but not COX-1 in human chondrocytes (HCH). Cells (PromoCell, Germany) were treated with three levels of genistein (0, 50, and 100 ?M). After one hour, the genistein-treated cells were stimulated by one μg/mL LPS for six hours. Cells were then harvested and the cytosolic fraction was isolated for assessing COX-1 and COX-2 protein levels using Western blot technique. Nitric oxide (NO), interleukin-I Beta (IL-1?), and YKL-40 productions were also measured in cell culture supernatants. NO, and IL-1? were measured as markers of inflammation and YKL-40 was assessed as a marker of cartilage catabolism. Interestingly, LG50 was more effective in reducing NO production than LG100 (42% vs. 28%) in comparison with LPS-treatred control cells. Genistein had no significant effect on either YKL-40 or IL-1? levels. Our data indicate that the LPS-stimulated increases in COX-2 protein level and NO in supernatant are reduced by pretreatment of genistein, whereas COX-1 protein level is not affected by genistein.
Advisors/Committee Members: Arjmandi, Bahram H. (advisor), Lucas, Edralin A. (committee member), Madihally, Sundar V. (committee member).
Subjects/Keywords: genistein; chondrocyte; inflammation
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APA (6th Edition):
Hooshmand-yazdi, S. (2006). Genistein Reduces Production of Proinflammatory Molecules in Human Chondrocytes. (Thesis). Oklahoma State University. Retrieved from http://hdl.handle.net/11244/9233
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hooshmand-yazdi, Shirin. “Genistein Reduces Production of Proinflammatory Molecules in Human Chondrocytes.” 2006. Thesis, Oklahoma State University. Accessed April 13, 2021.
http://hdl.handle.net/11244/9233.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hooshmand-yazdi, Shirin. “Genistein Reduces Production of Proinflammatory Molecules in Human Chondrocytes.” 2006. Web. 13 Apr 2021.
Vancouver:
Hooshmand-yazdi S. Genistein Reduces Production of Proinflammatory Molecules in Human Chondrocytes. [Internet] [Thesis]. Oklahoma State University; 2006. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/11244/9233.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hooshmand-yazdi S. Genistein Reduces Production of Proinflammatory Molecules in Human Chondrocytes. [Thesis]. Oklahoma State University; 2006. Available from: http://hdl.handle.net/11244/9233
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
Durand, Anne-Laure.
Rôle de l'épigénétique dans la régulation des collagènes dans les chondrocytes articulaires humains : nouveaux aspects pour la compréhension de l'homéostasie du cartilage : The role of epigenetics in the regulation of collagens in human articular chondrocytes : new insight for cartilage homeostasis.
Degree: Docteur es, Sciences de la vie, 2017, Lyon
URL: http://www.theses.fr/2017LYSE1270
► Le cartilage articulaire est un tissu avasculaire ayant une faible capacité de régénération. Ce tissu est essentiellement constitué d’un type cellulaire, les chondrocytes, inclus dans…
(more)
▼ Le cartilage articulaire est un tissu avasculaire ayant une faible capacité de régénération. Ce tissu est essentiellement constitué d’un type cellulaire, les chondrocytes, inclus dans une matrice extracellulaire abondante et de composition très spécifique. L’arthrose, la maladie touchant le cartilage la plus fréquente, est caractérisée par la perte progressive de cette matrice extracellulaire, ce qui conduit à l’érosion des surfaces articulaires. Les causes sont multiples et encore mal comprises: inflammation, génétique, mécanique etc... Plusieurs études ont récemment mis en évidence l’implication des mécanismes épigénétiques dans la réponse des chondrocytes aux cytokines inflammatoires (contribuant au catabolisme du tissu).Notre but a été d’étudier le rôle encore peu exploré de ces mécanismes dans la synthèse de la matrice extracellulaire du cartilage (contribuant à l'anabolisme). En utilisant des chondrocytes articulaires humains en culture primaire, nous avons identifié des marques de méthylation de l'ADN étroitement associées à l’expression de gènes codant les principaux composants de la matrice cartilagineuse. Ceci apporte un nouvel éclairage sur l’instabilité du phénotype chondrocytaire. De plus, nous décrivons pour la première fois l'implication de la lysine déméthylase LSD1 (une enzyme modifiant l'état de la chromatine dont l’expression est augmentée dans le cartilage arthrosique), dans la régulation génique d'un collagène du cartilage, le collagène de type IX. L’ensemble des résultats met en évidence de nouveaux mécanismes de régulation génique dans les chondrocytes articulaires, qui pourraient être impliqués dans le développement de l’arthrose
The articular cartilage is an avascular tissue displaying a very limited regenerative capacity. This tissue is mainly composed of one cell type, the chondrocytes, which are embedded within an abundant and highly specialized extracellular matrix. Osteoarthritis, which is the most common joint disease, is characterized by the progressive loss of that matrix, leading to the erosion of articular surface. The causes of this pathology are multiple (genetic, biomechanical, inflammatory…) and are still not fully understood. Several studies have recently highlighted the involvement of epigenetic mechanisms in the chondrocyte response to inflammatory cytokines (contributing to cartilage catabolism).The aim of our work was to investigate the unexplored role of the epigenetic mechanisms in the ability of chondrocytes to synthesize the cartilage-specific matrix (contributing to cartilage anabolism). Using primary culture of human articular chondrocytes, we identified a DNA methylation profile closely associated with the expression of the genes encoding the main structural components of the extracellular matrix. These findings bring new insights in the comprehension of chondrocyte phenotype instability. Moreover, we report for the first time the involvement of the lysine demethylase LSD1, a chromatin-modifying enzyme highly expressed in osteoarthritic tissue, in the gene…
Advisors/Committee Members: Lafont, Jérôme (thesis director).
Subjects/Keywords: LSD1; Méthylation de l'ADN; Cartilage; Chondrocyte; LSD1; DNA methylation; Cartilage; Chondrocyte; 571.6
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APA ·
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APA (6th Edition):
Durand, A. (2017). Rôle de l'épigénétique dans la régulation des collagènes dans les chondrocytes articulaires humains : nouveaux aspects pour la compréhension de l'homéostasie du cartilage : The role of epigenetics in the regulation of collagens in human articular chondrocytes : new insight for cartilage homeostasis. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2017LYSE1270
Chicago Manual of Style (16th Edition):
Durand, Anne-Laure. “Rôle de l'épigénétique dans la régulation des collagènes dans les chondrocytes articulaires humains : nouveaux aspects pour la compréhension de l'homéostasie du cartilage : The role of epigenetics in the regulation of collagens in human articular chondrocytes : new insight for cartilage homeostasis.” 2017. Doctoral Dissertation, Lyon. Accessed April 13, 2021.
http://www.theses.fr/2017LYSE1270.
MLA Handbook (7th Edition):
Durand, Anne-Laure. “Rôle de l'épigénétique dans la régulation des collagènes dans les chondrocytes articulaires humains : nouveaux aspects pour la compréhension de l'homéostasie du cartilage : The role of epigenetics in the regulation of collagens in human articular chondrocytes : new insight for cartilage homeostasis.” 2017. Web. 13 Apr 2021.
Vancouver:
Durand A. Rôle de l'épigénétique dans la régulation des collagènes dans les chondrocytes articulaires humains : nouveaux aspects pour la compréhension de l'homéostasie du cartilage : The role of epigenetics in the regulation of collagens in human articular chondrocytes : new insight for cartilage homeostasis. [Internet] [Doctoral dissertation]. Lyon; 2017. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2017LYSE1270.
Council of Science Editors:
Durand A. Rôle de l'épigénétique dans la régulation des collagènes dans les chondrocytes articulaires humains : nouveaux aspects pour la compréhension de l'homéostasie du cartilage : The role of epigenetics in the regulation of collagens in human articular chondrocytes : new insight for cartilage homeostasis. [Doctoral Dissertation]. Lyon; 2017. Available from: http://www.theses.fr/2017LYSE1270
21.
El-Hayek, Elissar.
Analyse à large échelle du profil d'expression des gènes dans des chondrocytes articulaires soumis à un stress mécanique de type étirement : la relaxine une nouvelle cible d'intérêt dans les pathologies ostéoarticulaires ? : Pas de titre traduit.
Degree: Docteur es, Biologie cellulaire et moléculaire, 2013, Université Paris Descartes – Paris V
URL: http://www.theses.fr/2013PA05T077
► Le cartilage articulaire est un tissu conjonctif spécialisé recouvrant les surfaces osseuses et assurant, avec d’autres tissus comme la membrane synoviale, le bon fonctionnement des…
(more)
▼ Le cartilage articulaire est un tissu conjonctif spécialisé recouvrant les surfaces osseuses et assurant, avec d’autres tissus comme la membrane synoviale, le bon fonctionnement des articulations. Le cartilage est composé d'un type cellulaire, le chondrocyte, qui assure la synthèse et la dégradation d’une matrice extracellulaire essentielle à ses propriétés mécaniques. Les articulations, en conditions physiologique et pathologique, sont soumises à deux stress principaux agissant sur l’homéostasie du cartilage : le stress mécanique et le stress inflammatoire. Le premier objectif de ma thèse était d’étudier l’effet d’un stress mécanique de type étirement sur le profil d’expression des gènes dans des chondrocytes articulaires de lapin en culture primaire en utilisant une approche à grande échelle (micro‐arrays). Nous avons identifié 36 et 57 transcrits répertoriés dans le génome de lapin et dont les taux d’expression sont respectivement augmentés et diminués par un étirement équibiaxial cyclique (5%, 1Hz, 20h). Certains gènes sont connus pour leur implication dans l’inflammation, la mort cellulaire et la dégradation matricielle. Parmi eux, celui de la relaxine (RLN) était le gène le plus induit par l’étirement. La relaxine, hormone peptidique de la superfamille de l’insuline/relaxine, est connue pour son implication dans la reproduction et la grossesse. En revanche son rôle dans le cartilage articulaire restait à étudier. Le deuxième objectif de ma thèse était, par conséquent, de caractériser la fonction de la RLN dans le cartilage. Mes résultats de RT‐PCR quantitative montrent pour la première fois que la quantité des transcrits de la RLN est augmentée par le stress mécanique et le stress inflammatoire (traitement par l’interleukine‐1) dans des chondrocytes articulaires de lapin. De plus, la quantité des transcrits de la RLN est diminuée au cours de la dédifférenciation des chondrocytes. Dans un modèle de gonarthrose induite chez la souris par déstabilisation du ménisque médial, j’ai montré par immunofluorescence que la RLN est principalement présente au niveau des couches superficielles du cartilage de genou et que son expression diminue dans le cartilage arthrosique par rapport au cartilage normal. De plus, le traitement par de la RLN de chondrocytes de lapin augmente l’activité de la métalloprotéinase MMP‐9 impliquées dans la dégradation du cartilage. En conclusion, cette étude montre que la RLN est sensible aux stress mécanique et inflammatoire et la dédifférenciation des chondrocytes. Elle suggère que cette hormone pourrait moduler l’homéostasie du cartilage. La RLN est donc une cible potentielle d’intérêt dans les pathologies ostéoarticulaires.
The articular cartilage is a specialized conjunctive tissue covering bone surfaces. It ensures, together with other tissues like the synovial membrane, the right functioning of the articulations. The cartilage is formed of one cellular type, the chondrocyte, which is responsible for the synthesis and degradation of the extracellular matrix required for its mechanical…
Advisors/Committee Members: Rannou, François (thesis director).
Subjects/Keywords: Chondrocyte; Étirement; Relaxine; Inflammation; Dédifférenciation; Arthrose; Chondrocyte; Stretching; Relaxin; Inflammation; Dedifferentiation; Osteoarthritis; 611.018 1
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APA (6th Edition):
El-Hayek, E. (2013). Analyse à large échelle du profil d'expression des gènes dans des chondrocytes articulaires soumis à un stress mécanique de type étirement : la relaxine une nouvelle cible d'intérêt dans les pathologies ostéoarticulaires ? : Pas de titre traduit. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2013PA05T077
Chicago Manual of Style (16th Edition):
El-Hayek, Elissar. “Analyse à large échelle du profil d'expression des gènes dans des chondrocytes articulaires soumis à un stress mécanique de type étirement : la relaxine une nouvelle cible d'intérêt dans les pathologies ostéoarticulaires ? : Pas de titre traduit.” 2013. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed April 13, 2021.
http://www.theses.fr/2013PA05T077.
MLA Handbook (7th Edition):
El-Hayek, Elissar. “Analyse à large échelle du profil d'expression des gènes dans des chondrocytes articulaires soumis à un stress mécanique de type étirement : la relaxine une nouvelle cible d'intérêt dans les pathologies ostéoarticulaires ? : Pas de titre traduit.” 2013. Web. 13 Apr 2021.
Vancouver:
El-Hayek E. Analyse à large échelle du profil d'expression des gènes dans des chondrocytes articulaires soumis à un stress mécanique de type étirement : la relaxine une nouvelle cible d'intérêt dans les pathologies ostéoarticulaires ? : Pas de titre traduit. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2013. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2013PA05T077.
Council of Science Editors:
El-Hayek E. Analyse à large échelle du profil d'expression des gènes dans des chondrocytes articulaires soumis à un stress mécanique de type étirement : la relaxine une nouvelle cible d'intérêt dans les pathologies ostéoarticulaires ? : Pas de titre traduit. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2013. Available from: http://www.theses.fr/2013PA05T077
Université de Lorraine
22.
Guibert, Mathilde.
Altération du phénotype chondrocytaire : Rôle de l’homéostasie locale de facteurs modulant la balance Pi/Ppi : Alteration in chondrocyte phenotype : role of local homeostasis of Pi/PPi balance modulating factors.
Degree: Docteur es, Sciences de la vie et de la santé, 2016, Université de Lorraine
URL: http://www.theses.fr/2016LORR0160
► L'arthrose (OA) est une maladie articulaire chronique qui résulte de changements complexes dans le phénotype des chondrocytes. La présence de microcristaux contenant du phosphate dans…
(more)
▼ L'arthrose (OA) est une maladie articulaire chronique qui résulte de changements complexes dans le phénotype des chondrocytes. La présence de microcristaux contenant du phosphate dans les zones de cartilage lésées suggère que le métabolisme phosphocalcique contribue en partie aux modifications du phénotype chondrocytaire au cours de la maladie. De nombreuses études ont montré que des concentrations élevées en Phosphate Inorganique extracellulaire (ePi) ou en PyroPhosphate Inorganique (ePPi) ont respectivement un effet activateur ou répressif sur la minéralisation du cartilage articulaire. Comme le Fibroblast Growth Factor 23 (FGF23) régule les concentrations de Pi, FGF23 semble être un candidat aux modifications phénotypiques observées dans l'OA. De plus, il a récemment été mis en évidence que l’ePPi prévient la dédifférenciation in vitro des chondrocytes articulaires chez le rat, un effet provoqué par la production de PPi par la protéine Ank. Cela suggère que l’ePPi pourrait être un candidat pour prévenir les modifications du phénotype chondrocytaire. Premièrement, nous avons montré que l’expression de FGF23 est plus importante dans du cartilage lésé que dans du cartilage sain. Sous stimulation croissante de FGF23, les chondrocytes humains OA présentent une expression soutenue des marqueurs d’hypertrophie tels que COL10A1, VEGF et MMP13. Nous avons également démontré que l’expression de MMP13 est fortement dépendante de FGFR1 mais indépendante de Klotho et qu’elle est fortement régulée par la voie MEK/ERK et dans une moindre mesure par la voie PI3K/AKT. Deuxièmement, nous avons montré que FGF23 est produit de façon plus importante au cours de la différenciation des ATDC5 et qu’une stimulation par FGF23 augmente la minéralisation et l’expression des marqueurs d’hypertrophie, et ce, d’autant plus fortement en présence d’une stimulation par du Pi dans ces cellules. Dans la seconde partie, nous avons montré que des chondrocytes humains OA stimulés par du PPi présentent une expression diminuée des composants collagéniques de la matrice et une expression augmentée des MMPs, de la fibronectine et des intégrines. Une stimulation par le PPi active de façon importante la voie p38 et dans une moindre mesure la voie ERK pour réguler l’expression de ses gènes cibles et notamment MMP13 d’une manière Ank indépendante. Enfin, nous avons démontré qu’une stimulation par FGF23 entraine une augmentation de l’expression de Pit-1, ENPP1 et ANK ainsi que la production de PPi par les chondrocytes humains OA. Les résultats obtenus dans cette étude démontrent que le FGF23 permet localement une différenciation des chondrocytes OA vers un phénotype hypertrophique et peut potentiellement être considéré comme un facteur aggravant de l’OA. Contrairement aux données préliminaires chez le rat, le PPi permet un remodelage matriciel des chondrocytes humains OA et pourrait potentiellement contribuer aux effets pro-hypertrophiques du FGF23
Osteoarthritis (OA) is the most common form of chronic joint disease, characterized by cartilage degeneration…
Advisors/Committee Members: Bianchi, Arnaud (thesis director), Kempf, Hervé (thesis director).
Subjects/Keywords: Chondrocyte; Phénotype; Pyrophosphate inorganique; Phosphate inorganique; FGF23; Arthrose; Chondrocyte; Phenotype; Inorganic pyrophosphate; Inorganic phosphate; FGF23; Osteoarthritis; 571.75; 616.722 3; 612.392 4
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APA (6th Edition):
Guibert, M. (2016). Altération du phénotype chondrocytaire : Rôle de l’homéostasie locale de facteurs modulant la balance Pi/Ppi : Alteration in chondrocyte phenotype : role of local homeostasis of Pi/PPi balance modulating factors. (Doctoral Dissertation). Université de Lorraine. Retrieved from http://www.theses.fr/2016LORR0160
Chicago Manual of Style (16th Edition):
Guibert, Mathilde. “Altération du phénotype chondrocytaire : Rôle de l’homéostasie locale de facteurs modulant la balance Pi/Ppi : Alteration in chondrocyte phenotype : role of local homeostasis of Pi/PPi balance modulating factors.” 2016. Doctoral Dissertation, Université de Lorraine. Accessed April 13, 2021.
http://www.theses.fr/2016LORR0160.
MLA Handbook (7th Edition):
Guibert, Mathilde. “Altération du phénotype chondrocytaire : Rôle de l’homéostasie locale de facteurs modulant la balance Pi/Ppi : Alteration in chondrocyte phenotype : role of local homeostasis of Pi/PPi balance modulating factors.” 2016. Web. 13 Apr 2021.
Vancouver:
Guibert M. Altération du phénotype chondrocytaire : Rôle de l’homéostasie locale de facteurs modulant la balance Pi/Ppi : Alteration in chondrocyte phenotype : role of local homeostasis of Pi/PPi balance modulating factors. [Internet] [Doctoral dissertation]. Université de Lorraine; 2016. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2016LORR0160.
Council of Science Editors:
Guibert M. Altération du phénotype chondrocytaire : Rôle de l’homéostasie locale de facteurs modulant la balance Pi/Ppi : Alteration in chondrocyte phenotype : role of local homeostasis of Pi/PPi balance modulating factors. [Doctoral Dissertation]. Université de Lorraine; 2016. Available from: http://www.theses.fr/2016LORR0160
Université de Lorraine
23.
Xie, Zhe.
Wnt signaling in human cartilage degeneration and chondrocytes de-differentiation : La signalisation de Wnt dans la dégradation du cartilage et la dédifférenciation chondrocytaire.
Degree: Docteur es, Sciences de la vie et de la santé, 2016, Université de Lorraine
URL: http://www.theses.fr/2016LORR0111
► La dérégulation de la signalisation Wnt est impliquée dans les anomalies du développement et dans la pathogenèse de nombreuses maladies, y compris l'arthrose. Au cours…
(more)
▼ La dérégulation de la signalisation Wnt est impliquée dans les anomalies du développement et dans la pathogenèse de nombreuses maladies, y compris l'arthrose. Au cours de ce travail, nous avons étudié l'effet de Wnt-3a sur l’ADAMTS-4 dans les explants de cartilage et les chondrocytes primaires humains. Nous avons observé que Wnt-3a régule négativement l'expression de cette agrecanase et avons démontré que cette inhibition est médiée par Frizzled-8 via l’activation de la voie canonique et inhibition de l'activité de NFκB. En outre, nous avons montré que Wnt-3a est capable de s’opposer à l'induction de l’expression de l’ADAMTS-4 par l'IL-1ß, indiquant que la voie Wnt/ß-caténine peut jouer un rôle protecteur dans l'arthrose. D'autre part, la signalisation non canonique de Wnt induit une perte de la stabilité phénotypique des chondrocytes articulaires qui représente un événement précoce dans l'arthrose, cependant les mécanismes impliqués restent à élucider. Au cours de ce travail, nous avons identifié la cascade Wnt/CaMKII/B-raf/ERK1/2 comme voie de signalisation non-canonique modulant le phénotype chondrocytaire et avons montré que le syndécane4 est un composant essentiel. Nous avons démontré qu’en réponse à Wnt-3a, Frizzled-6 active la voie ERK1/2 en induisant la fixation de la kinase CaMKIIα au syndécane4 et celle de B-Raf à DVL-2 conduisant à l'activation de B-Raf. Dans une boucle de rétrocontrôle, Wnt-3a inhibe l’expression du syndécane4. Ce travail révèle le rôle du syndécane4 dans la régulation du phénotype chondrocytaire et met en évidence de nouvelles cibles qui peuvent avoir un potentiel thérapeutique contre l'arthrose
Dysregulation of Wnt signaling has been implicated in developmental defects and in the pathogenesis of many diseases, including osteoarthritis. Here, we studied the effect of Wnt-3a on ADAMTS-4 in human cartilage explants and primary chondrocytes and found that Wnt-3a negatively regulates the expression of this aggrecanase. We demonstrated that Wnt-3a inhibition of ADAMTS-4 expression is mediated by Frizzled-8 through activation of the canonical Wnt/ß-catenin pathway leading to inhibition of NFκB activity and down-regulation of ADAMTS-4. Furthermore, we showed that Wnt-3a is able to counteract the induction of ADAMTS-4 by IL-1ß, therefore indicating that Wnt/ß-catenin pathway may play a protective role in osteoarthritis. On the other hand, Non-canonical Wnt signaling induces loss of phenotypic stability of articular chondrocytes which represents an early event in osteoarthritis, but the underlying mechanisms are poorly understood. In this thesis, we identify Wnt/CaMKII/B-raf/ERK1/2 cascade as non-canonical signaling pathway that modulates chondrocyte phenotype and revealed that syndecan4 is an essential component of this pathway. We show that in response to Wnt-3a, Fz-6 activates non-canonical signaling by triggering the docking of CaMKIIα to syndecan4 and that of B-raf to DVL-2 leading to the activation of B-raf that transduces signals to ERK1/2 MAPK. In a feedback loop, non-canonical Wnt…
Advisors/Committee Members: Ouzzine, Mohamed (thesis director).
Subjects/Keywords: Wnt; Syndécane4; Chondrocyte; Différenciation; ADAMTS-4; Arthrose; Wnt; Syndecan4; Chondrocyte; Differentiation; ADAMTS-4; Osteoarthritis; 616.722 3; 611.018 1
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APA ·
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APA (6th Edition):
Xie, Z. (2016). Wnt signaling in human cartilage degeneration and chondrocytes de-differentiation : La signalisation de Wnt dans la dégradation du cartilage et la dédifférenciation chondrocytaire. (Doctoral Dissertation). Université de Lorraine. Retrieved from http://www.theses.fr/2016LORR0111
Chicago Manual of Style (16th Edition):
Xie, Zhe. “Wnt signaling in human cartilage degeneration and chondrocytes de-differentiation : La signalisation de Wnt dans la dégradation du cartilage et la dédifférenciation chondrocytaire.” 2016. Doctoral Dissertation, Université de Lorraine. Accessed April 13, 2021.
http://www.theses.fr/2016LORR0111.
MLA Handbook (7th Edition):
Xie, Zhe. “Wnt signaling in human cartilage degeneration and chondrocytes de-differentiation : La signalisation de Wnt dans la dégradation du cartilage et la dédifférenciation chondrocytaire.” 2016. Web. 13 Apr 2021.
Vancouver:
Xie Z. Wnt signaling in human cartilage degeneration and chondrocytes de-differentiation : La signalisation de Wnt dans la dégradation du cartilage et la dédifférenciation chondrocytaire. [Internet] [Doctoral dissertation]. Université de Lorraine; 2016. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2016LORR0111.
Council of Science Editors:
Xie Z. Wnt signaling in human cartilage degeneration and chondrocytes de-differentiation : La signalisation de Wnt dans la dégradation du cartilage et la dédifférenciation chondrocytaire. [Doctoral Dissertation]. Université de Lorraine; 2016. Available from: http://www.theses.fr/2016LORR0111
24.
Roszkowska, Monika.
Mécanismes moléculaires de la transdifférenciation des cellules musculaires lisses et calcification dans l'athérosclérose : Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis.
Degree: Docteur es, Biochimie, 2018, Lyon; Instytut biologii doświadczalnej im. M. Nenckiego (Pologne)
URL: http://www.theses.fr/2018LYSE1059
► Chez les patients atteints d'athérosclérose, les calcifications vasculaires sont une caracteristique des plaques d'athérome. Elles résultent de la trans-différenciation des cellules musculaires lisses (CMLs) en…
(more)
▼ Chez les patients atteints d'athérosclérose, les calcifications vasculaires sont une caracteristique des plaques d'athérome. Elles résultent de la trans-différenciation des cellules musculaires lisses (CMLs) en cellules de type ostéoblastique et/ou chondrocytaire, notamment en réponse à des cytokines inflammatoires. Les CMLs forment alors des cristaux par l'activité de la phosphatase alcaline non-spécifique du tissu (TNAP). A la lumière de résultats récents, nous avons émis l'hypothèse que la TNAP module la trans-différenciation des CMLs. Nos objectifs étaient donc de déterminer l'effet de la TNAP dans la trans-différenciation des CMLs, et d'étudier les mécanismes impliqués dans son induction. Nous avons observé que l'ajout de phosphatase alcaline purifiée ou la surexpression de TNAP stimule l'expression de marqueurs chondrocytaires en culture de CMLs et de cellules souches mésenchymateuses. De plus, l'inhibition de la TNAP bloque la maturation de chondrocytes primaires. Nous avons observé un rôle des cristaux formés par la TNAP, puisque l'ajout de cristaux seuls ou associés à une matrice collagénique a reproduit les effets de la TNAP. Nous suspectons que la TNAP agit en hydrolysant le PPi et en générant des cristaux. Ces cristaux ensuite induisent l'expression du facteur ostéogénique BMP-2 et l'inhibition des effets de la BMP-2 annule les effets de la TNAP. De plus, nous étions intéressés par les la localisation et la fonction de marqueurs de minéralisation comme les annexines en parallèle de la TNAP. Nous avons observé que l'activité TNAP des CMLs induit la minéralisation en grande partie quand la TNAP est associée aux vésicules matricielles et au fibres de collagène
Vascular calcification (VC) is a hallmark of atherosclerosis plaques. Calcification (formation of apatite) of advanced lesions share common features with endochondral ossification of long bones and appears to stabilize plaques. This process is associated with trans-differentiation of vascular smooth muscle cells (VSMCs) into chondrocyte-like cells. On the other hand, microcalcification of early plaques, which is poorly understood, is thought to be harmful. The two proteins necessary for physiological mineralization are tissue-nonspecific alkaline phosphatase (TNAP) and collagen. Under pathological conditions, TNAP is activated by inflammatory cytokines in VSMCs, whereas collagen is produced constantly. The activation of TNAP appears to induce calcification of these cells. Therefore, the objective of this PhD thesis was to study the role of TNAP and generated apatite crystals in the VSMC trans-differentiation and determine underlying molecular mechanisms. Based on the obtained results, we propose that activation of BMP-2, a strong inducer of ectopic calcification, and formation of apatite crystals generated by TNAP represents a likely mechanism responsible for stimulation of VSMC trans-differentiation. Moreover, we were interested in localization and function of mineralization markers such as TNAP and annexins in mineralization process mediated by…
Advisors/Committee Members: Magne, David (thesis director), Pikula, Slawomir (thesis director).
Subjects/Keywords: Cellule musculaire lisse; Phosphatase alcaline; Calcification vasculaire; Chondrocyte; Vascular smooth muscle cell; Tissue-nonspecific alkaline phosphatase; Vascular calcification; Chondrocyte; 572
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APA (6th Edition):
Roszkowska, M. (2018). Mécanismes moléculaires de la transdifférenciation des cellules musculaires lisses et calcification dans l'athérosclérose : Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis. (Doctoral Dissertation). Lyon; Instytut biologii doświadczalnej im. M. Nenckiego (Pologne). Retrieved from http://www.theses.fr/2018LYSE1059
Chicago Manual of Style (16th Edition):
Roszkowska, Monika. “Mécanismes moléculaires de la transdifférenciation des cellules musculaires lisses et calcification dans l'athérosclérose : Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis.” 2018. Doctoral Dissertation, Lyon; Instytut biologii doświadczalnej im. M. Nenckiego (Pologne). Accessed April 13, 2021.
http://www.theses.fr/2018LYSE1059.
MLA Handbook (7th Edition):
Roszkowska, Monika. “Mécanismes moléculaires de la transdifférenciation des cellules musculaires lisses et calcification dans l'athérosclérose : Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis.” 2018. Web. 13 Apr 2021.
Vancouver:
Roszkowska M. Mécanismes moléculaires de la transdifférenciation des cellules musculaires lisses et calcification dans l'athérosclérose : Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis. [Internet] [Doctoral dissertation]. Lyon; Instytut biologii doświadczalnej im. M. Nenckiego (Pologne); 2018. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2018LYSE1059.
Council of Science Editors:
Roszkowska M. Mécanismes moléculaires de la transdifférenciation des cellules musculaires lisses et calcification dans l'athérosclérose : Molecular mechanisms of vascular smooth muscle cell trans-differentiation and calcification in atherosclerosis. [Doctoral Dissertation]. Lyon; Instytut biologii doświadczalnej im. M. Nenckiego (Pologne); 2018. Available from: http://www.theses.fr/2018LYSE1059
25.
Bouderlique, Thibault.
Etude des propriétés ostéoinductrices et chondroinductrices de "l'Heparin affin regulatory peptide" sur les cellules stromales mésenchymateuses humaines, application en régénération osseuse : Study of the osteoinductive and chondroinductive properties of the heparin affin regulatory peptide on human mesenchymal stromal cells, application in bone regeneration.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2012, Université Paris-Est
URL: http://www.theses.fr/2012PEST0063
► La régénération osseuse est un processus impliquant de nombreux types cellulaires comme les ostéoblastes, les chondrocytes ou les cellules stromales mésenchymateuses (CSM). Les CSM possèdent…
(more)
▼ La régénération osseuse est un processus impliquant de nombreux types cellulaires comme les ostéoblastes, les chondrocytes ou les cellules stromales mésenchymateuses (CSM). Les CSM possèdent des capacités de différenciation suggérant leur implication dans ce processus de réparation. La régénération osseuse est le fruit de la coordination complexe de l'activité de nombreux facteurs de croissance. Parmi eux, l'« Heparin affin regulatory peptide » (HARP) est fortement exprimé dans le callus durant la régénération mais son rôle n'est pas clairement établi. Le but de ce travail de thèse a été (1) d'évaluer les effets de HARP sur les propriétés de migration, de prolifération et de différenciation des CSM in vitro ; (2) évaluer la capacité de HARP à induire une formation osseuse ou une régénération osseuse in vivo.Nos résultats démontrent que HARP est chémoattractant pour les CSM et potentialise leur prolifération. De plus, nous montrons pour la première fois que le traitement de CSM par HARP durant leur chondroinduction conduit à une différenciation chondrocytaire de type hypertrophique. Ce type cellulaire est primordial dans les derniers stades de la formation osseuse endochondrale qui se met en place durant la croissance osseuse, mais également durant la réparation. L'implantation de biomatériaux associés à HARP dans un défaut osseux de condyle fémoral a conduit à la formation de cartilage et d'os dans l'implant, reproduisant le mécanisme physiologique de formation osseuse endochondrale. Le biomatériau seul n'a été envahi que par du tissu fibreux.Durant les processus de réparation tissulaire, les glycosaminoglycannes (GAG), des chaînes polysaccharidiques sulfatées, composants majeurs de la matrice extracellulaire, participent à la modulation des effets des facteurs de croissance durant la réparation. Récemment, des mimétiques structuraux et fonctionnels des GAG ont été développés. Durant ma thèse, j'ai été associé au travail d'un doctorant de l'équipe de P.Albanese, qui a montré que des mimétiques de GAG induisent une différenciation ostéoblastique des CSM en l'absence de traitement ostéoinducteur. L'implantation sous-cutanée de biomatériaux covalemment associés aux mimétiques ont également été menées, et ont permis d'observer des potentialisations des processus de vascularisation de l'implant et de l'activité ostéoclastique. Ces resultats ont permis de valider l'interêt des GAG mimétiques dans le cadre des thérapies de régénération osseuse.Cette étude démontre pour la première fois les effets chondroinducteurs directs de HARP sur la production de molécules de la matrice cartilagineuse par les CSM in vitro, mais également sur la synthèse de tissu cartilagineux in vivo. Les effets de HARP observés sur la régénération osseuse confirment qu'il pourrait être un bon candidat en chirurgie orthopédique en permettant une régénération de type endochondrale typique de la réparation physiologique. De plus les nouvelles stratégies developpées dans le laboratoire sur la fonctionnalisation covalente de biomateriaux par des GAG…
Advisors/Committee Members: Albanese, Patricia (thesis director).
Subjects/Keywords: Cellules souches mesenchymateuses; Harp; Ostéoblaste; Chondrocyte; Biomatériaux; Réparation osseuse; Mesenchymal stem cell; Harp; Osteoblast; Chondrocyte; Biomaterials; Bone repair
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APA ·
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MLA ·
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CSE |
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APA (6th Edition):
Bouderlique, T. (2012). Etude des propriétés ostéoinductrices et chondroinductrices de "l'Heparin affin regulatory peptide" sur les cellules stromales mésenchymateuses humaines, application en régénération osseuse : Study of the osteoinductive and chondroinductive properties of the heparin affin regulatory peptide on human mesenchymal stromal cells, application in bone regeneration. (Doctoral Dissertation). Université Paris-Est. Retrieved from http://www.theses.fr/2012PEST0063
Chicago Manual of Style (16th Edition):
Bouderlique, Thibault. “Etude des propriétés ostéoinductrices et chondroinductrices de "l'Heparin affin regulatory peptide" sur les cellules stromales mésenchymateuses humaines, application en régénération osseuse : Study of the osteoinductive and chondroinductive properties of the heparin affin regulatory peptide on human mesenchymal stromal cells, application in bone regeneration.” 2012. Doctoral Dissertation, Université Paris-Est. Accessed April 13, 2021.
http://www.theses.fr/2012PEST0063.
MLA Handbook (7th Edition):
Bouderlique, Thibault. “Etude des propriétés ostéoinductrices et chondroinductrices de "l'Heparin affin regulatory peptide" sur les cellules stromales mésenchymateuses humaines, application en régénération osseuse : Study of the osteoinductive and chondroinductive properties of the heparin affin regulatory peptide on human mesenchymal stromal cells, application in bone regeneration.” 2012. Web. 13 Apr 2021.
Vancouver:
Bouderlique T. Etude des propriétés ostéoinductrices et chondroinductrices de "l'Heparin affin regulatory peptide" sur les cellules stromales mésenchymateuses humaines, application en régénération osseuse : Study of the osteoinductive and chondroinductive properties of the heparin affin regulatory peptide on human mesenchymal stromal cells, application in bone regeneration. [Internet] [Doctoral dissertation]. Université Paris-Est; 2012. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2012PEST0063.
Council of Science Editors:
Bouderlique T. Etude des propriétés ostéoinductrices et chondroinductrices de "l'Heparin affin regulatory peptide" sur les cellules stromales mésenchymateuses humaines, application en régénération osseuse : Study of the osteoinductive and chondroinductive properties of the heparin affin regulatory peptide on human mesenchymal stromal cells, application in bone regeneration. [Doctoral Dissertation]. Université Paris-Est; 2012. Available from: http://www.theses.fr/2012PEST0063
26.
Drevet, Sabine.
Evaluation d'outils pour l'étude de l'arthrose à l'échelle protéique, cellulaire et animale : Evaluation of tools for the study of osteoarthritis at the protein, cellular and animal level.
Degree: Docteur es, Biologie cellulaire, 2020, Université Grenoble Alpes
URL: http://www.theses.fr/2020GRALV019
► L’arthrose est une pathologie chronique dégénérative invalidante, fréquente, multifactorielle, grave et coûteuse. Deux avancées conceptuelles récentes soulignent une vision pluritissulaire de la maladie et un…
(more)
▼ L’arthrose est une pathologie chronique dégénérative invalidante, fréquente, multifactorielle, grave et coûteuse. Deux avancées conceptuelles récentes soulignent une vision pluritissulaire de la maladie et un abord clinique phénotypique, permettant d’envisager l’individualisation de la stratégie thérapeutique. Un article publié dans la Revue de Gériatrie résume brièvement ces deux concepts. Sur le plan physiopathologique, le chondrocyte est la cellule cible primordiale et la NADPH Oxydase (Nox) 4 semble être un acteur d’intérêt. La Nox4, son activité, son interaction avec ses partenaires et sa conformation constituent des enjeux scientifiques d’intérêt et autant de cibles thérapeutiques potentielles pour l’élaboration de stratégies thérapeutiques anti-arthrosiques. Au cours de ce travail de thèse, le lien entre Nox4 et arthrose était abordé à 3 niveaux : structural, cellulaire et animal. Le volet structural laisse supposer que la boucle E de Nox4 est une séquence intrinsèquement désordonnée. Ainsi, la fonction de Nox4 pourrait être liée à sa structure, venant ainsi corroborer l’hypothèse de la « cage redox » avec une production de peroxyde d’hydrogène par dismutation spontanée. Les connaissances actuelles sur l’implication du stress oxydant et particulièrement de la Nox4 dans l’arthrose ont été étudiées au cours d’une publication dans Experimental and Gerontology. Ensuite, le volet cellulaire confirmait que la Nox4 est exprimée par le chondrocyte primaire humain et notre hypothèse d’une voie de signalisation catabolique IGF-1/Nox4 n’a pas été invalidée. Le volet animal a été l’occasion de faire une revue des connaissances tant sur les différents modèles murins d’arthrose que sur les critères d’évaluation clinique et paraclinique avec notamment des innovations technologiques. Cet article est en cours de révision majeure dans Bone Research. Notre travail expérimental a par ailleurs montré que le cartilage murin exprimait les isoformes Nox2 et Nox4, et nos résultats sont en accord avec la littérature récente. Nous avons pour finir évalué un nouveau modèle d’arthrose murin selon des critères de jugement robustes et novateurs. Le modèle a été choisi dans la perspective de tester l’implication de Nox4 dans la voie de signalisation de l’IL-1β in vivo. Cet article sera soumis dans Bone Research.
Osteoarthritis (OA) is a chronic degenerative disease affecting millions of people around the world and one of the most co-occurring diseases among patients aged 55 years and older. Two recent conceptual approaches highlighted a pluritissular vision of the disease and a phenotypic clinical approach, making it possible to envisage individualization of the therapeutic strategy. An article published in the Revue de Gériatrie briefly summarizes these two concepts. The chondrocyte is the target cell and NADPH Oxidase (Nox) 4 is a player of interest in the physiopathological process of osteoarthritis. Nox4, its activity, its interaction with its partners and its conformation constitute scientific issues of interest and potential…
Advisors/Committee Members: Lardy, Bernard (thesis director), Gavazzi, Gaëtan (thesis director).
Subjects/Keywords: Arthrose; Chondrocyte; NADPH oxidase 4; Stress oxydant; Modèle; Animal; Osteoarthritis; Chondrocyte; NADPH oxidase 4; Oxidative stress; Model; Animal; 610
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APA (6th Edition):
Drevet, S. (2020). Evaluation d'outils pour l'étude de l'arthrose à l'échelle protéique, cellulaire et animale : Evaluation of tools for the study of osteoarthritis at the protein, cellular and animal level. (Doctoral Dissertation). Université Grenoble Alpes. Retrieved from http://www.theses.fr/2020GRALV019
Chicago Manual of Style (16th Edition):
Drevet, Sabine. “Evaluation d'outils pour l'étude de l'arthrose à l'échelle protéique, cellulaire et animale : Evaluation of tools for the study of osteoarthritis at the protein, cellular and animal level.” 2020. Doctoral Dissertation, Université Grenoble Alpes. Accessed April 13, 2021.
http://www.theses.fr/2020GRALV019.
MLA Handbook (7th Edition):
Drevet, Sabine. “Evaluation d'outils pour l'étude de l'arthrose à l'échelle protéique, cellulaire et animale : Evaluation of tools for the study of osteoarthritis at the protein, cellular and animal level.” 2020. Web. 13 Apr 2021.
Vancouver:
Drevet S. Evaluation d'outils pour l'étude de l'arthrose à l'échelle protéique, cellulaire et animale : Evaluation of tools for the study of osteoarthritis at the protein, cellular and animal level. [Internet] [Doctoral dissertation]. Université Grenoble Alpes; 2020. [cited 2021 Apr 13].
Available from: http://www.theses.fr/2020GRALV019.
Council of Science Editors:
Drevet S. Evaluation d'outils pour l'étude de l'arthrose à l'échelle protéique, cellulaire et animale : Evaluation of tools for the study of osteoarthritis at the protein, cellular and animal level. [Doctoral Dissertation]. Université Grenoble Alpes; 2020. Available from: http://www.theses.fr/2020GRALV019
Universiteit Utrecht
27.
Laar, A.M. van.
The effect of intra-articular pressure and mechanical load on articular chondrocyte cellular signalling.
Degree: 2012, Universiteit Utrecht
URL: http://dspace.library.uu.nl:8080/handle/1874/255225
► The various forms of joint loading have been found to differentially influence anatomical and molecular responses, which together are aimed to maintain the joint homeostasis.…
(more)
▼ The various forms of joint loading have been found to differentially influence anatomical and molecular responses, which together are
aimed to maintain the joint homeostasis. To elucidate these mechanisms of mechanotransduction, we review the roles of the distinct joint
components, as well as numerous in vitro studies that have been performed to unravel
chondrocyte responses in changing environments.
The main signalling pathways in transduction of load signals are initiated by integrins sensing matrix deformation and by altered interstitial
pH, influencing ion fluxes through membrane channels. Downstream signalling after static compression occurs mainly via the MAPK
pathways of ERK1/2, SAPK (Jnk) and p38, which directly influence transcription factors of genes involved in cartilage breakdown. In
contrast, cyclic compression and mild shear forces lead to membrane hyperpolarisation and subsequently stimulates cartilage matrix
synthesis. These findings add further comprehension with regard to the satisfactory clinical outcomes of joint distraction in osteoarthritic
(OA) joints. It has been shown that these joints contained repaired cartilage after treatment in animal models. Using improved in vivo
models in further research would allow a more thorough understanding of the underlying molecular processes of this reparative capacity of
damaged cartilage, which could lead to improved arthropathy treatment options.
Advisors/Committee Members: Mastbergen, S.C..
Subjects/Keywords: articular; cartilage; chondrocyte; load; mechanical; stress; pressure; diarthrodial; joint; subchondral
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APA ·
Chicago ·
MLA ·
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CSE |
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APA (6th Edition):
Laar, A. M. v. (2012). The effect of intra-articular pressure and mechanical load on articular chondrocyte cellular signalling. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/255225
Chicago Manual of Style (16th Edition):
Laar, A M van. “The effect of intra-articular pressure and mechanical load on articular chondrocyte cellular signalling.” 2012. Masters Thesis, Universiteit Utrecht. Accessed April 13, 2021.
http://dspace.library.uu.nl:8080/handle/1874/255225.
MLA Handbook (7th Edition):
Laar, A M van. “The effect of intra-articular pressure and mechanical load on articular chondrocyte cellular signalling.” 2012. Web. 13 Apr 2021.
Vancouver:
Laar AMv. The effect of intra-articular pressure and mechanical load on articular chondrocyte cellular signalling. [Internet] [Masters thesis]. Universiteit Utrecht; 2012. [cited 2021 Apr 13].
Available from: http://dspace.library.uu.nl:8080/handle/1874/255225.
Council of Science Editors:
Laar AMv. The effect of intra-articular pressure and mechanical load on articular chondrocyte cellular signalling. [Masters Thesis]. Universiteit Utrecht; 2012. Available from: http://dspace.library.uu.nl:8080/handle/1874/255225
University of Rochester
28.
Shen, Run; Chen, Di (1955 - ).
Regulation of Runx2 protein stability in chondrocyte
development.
Degree: PhD, 2009, University of Rochester
URL: http://hdl.handle.net/1802/6536
► During endochondral bone formation, cartilages provide the template for vascular invasion, which brings in osteoblasts to deposit bone matrix on the debris of apoptotic chondrocytes.…
(more)
▼ During endochondral bone formation, cartilages
provide the template for vascular invasion, which brings in
osteoblasts to deposit bone matrix on the debris of apoptotic
chondrocytes. Chondrocytes are basic building units of cartilage.
Their proliferation and differentiation direct the development of
cartilage, by first generating a sufficient number of chondrocytes
and then switching to many mature protein mills. PTHrP is one of
the essential growth factors which coordinate the whole cartilage
developmental program, so that cartilage achieves proper size and
maturation state at different stages. PTHrP has been reported to
promote chondrocyte proliferation by upregulating cyclin D1 gene
expression and preventing chondrocyte differentiation, while the
molecular mechanism of these regulations is largely unknown. To
understand this, we conducted both in vitro biochemical and in vivo
genetic studies. Runx2 is a critical transcriptional factor which
promotes chondrocyte maturation. By protein sequence analysis and
biochemical mapping for critical domains, we identified serine 472
at the C-terminal of Runx2 is a potential phosphorylation site by
cyclin D1/CDK4 complex, and its phosphorylation is essential for
inducing Runx2 protein turnover. Mutation of this serine to alanine
abolished the phosphorylation of Runx2 and made it resistant to
cyclin D1-induced protein turnover, and correlated with higher
protein stability of Runx2. In vivo, we demonstrated that PTHrP
treatment of chondrocytes correlates with a decrease of Runx2
protein level. The growth plate of the cyclin D1 knockout mouse
showed a much smaller proliferative zone and advanced maturation at
hypertrophic zone. Chondrocytes isolated from cyclin D1 null mice
showed higher protein level of Runx2 and lost response to PTHrP
stimulation. In summary, PTHrP prevents chondrocyte maturation by
inducing Runx2 protein turnover through upregulation of cyclin
D1/CDK4 activity. The proliferation and differentiation of
chondrocytes are inversely correlated in cartilage development, and
this study first provides a molecular mechanism of how
proliferation and differentiation are coordinated through protein
phosphorylation, ubiquitin-dependent degradation.
Subjects/Keywords: Ubiquitin; Runx2; Chondrocyte; PTHrP; Cartilage
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APA ·
Chicago ·
MLA ·
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CSE |
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Manager
APA (6th Edition):
Shen, Run; Chen, D. (. -. ). (2009). Regulation of Runx2 protein stability in chondrocyte
development. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/6536
Chicago Manual of Style (16th Edition):
Shen, Run; Chen, Di (1955 - ). “Regulation of Runx2 protein stability in chondrocyte
development.” 2009. Doctoral Dissertation, University of Rochester. Accessed April 13, 2021.
http://hdl.handle.net/1802/6536.
MLA Handbook (7th Edition):
Shen, Run; Chen, Di (1955 - ). “Regulation of Runx2 protein stability in chondrocyte
development.” 2009. Web. 13 Apr 2021.
Vancouver:
Shen, Run; Chen D(-). Regulation of Runx2 protein stability in chondrocyte
development. [Internet] [Doctoral dissertation]. University of Rochester; 2009. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1802/6536.
Council of Science Editors:
Shen, Run; Chen D(-). Regulation of Runx2 protein stability in chondrocyte
development. [Doctoral Dissertation]. University of Rochester; 2009. Available from: http://hdl.handle.net/1802/6536
University of Rochester
29.
Kotelsky, Alexander.
Elucidating the factors that govern vulnerability of in
situ articular chondrocytes to mechanical loading.
Degree: PhD, 2020, University of Rochester
URL: http://hdl.handle.net/1802/35670
► Articular cartilage (AC) is a load bearing tissue that covers and protects bones in synovial joints. Since resident cells (chondrocytes) in cartilage bear the responsibility…
(more)
▼ Articular cartilage (AC) is a load bearing tissue
that covers and protects bones in synovial joints.
Since resident
cells (chondrocytes) in cartilage bear the responsibility of
synthesizing and
maintaining the extracellular matrix (ECM),
preservation of chondrocyte viability is essential for
tissue
homeostasis and for successful tissue healing after restorative
clinical procedures.
Unfortunately, when cartilage is exposed to
abnormal mechanical loads in vivo (e.g., during and
after a major
joint injury), chondrocyte loss may occur, potentially leading to
the irreversible
breakdown of AC in the form of osteoarthritis
(OA). Additionally, during osteochondral graft
procedures aimed at
repairing focal cartilage defects, high impact forces required for
the graft
insertion induce iatrogenic cell death, thereby
increasing risk of graft failure. However, knowledge
remains
limited regarding how chondrocyte viability is affected by specific
cellular characteristics
(e.g., volume), tissue characteristics
(e.g., Young’s modulus) and features of the external loading
environment (e.g., type, magnitude and timescale of loading).
Therefore, the objective of this
research was to elucidate the
factors that govern the sensitivity of chondrocytes to two
different
forms of loading: impact and sub-impact. Based on
circumstantial evidence from previous studies,
we hypothesize that
initial chondrocyte volume is a key driving factor governing the
vulnerability
and survival of articular chondrocytes under impact
loading, but not under sub-impact loading. We
further hypothesize
that in situ chondrocyte vulnerability is influenced by gender and
increases with
load magnitude, load duration, impact energy and
age. To test these hypotheses, we established
and rigorously
characterized in vitro, in situ and in vivo murine injury models,
facilitating the
quantification of the spatial extent of
chondrocyte injury/death after controlled loading regimens.
We
also developed a novel method for determining the material
properties of mouse cartilage,
enabling delineation of changes in
inherent cell vulnerability from changes in ECM mechanical
properties. Our studies revealed a strong correlation between cell
volume and cell injury/death
under impact loading conditions that
was independent of the applied volume-perturbing method,
suggesting that reduction in cell volume is chondroprotective. In
contrast, under sub-impact loading the extent of cell injury/death
was correlated with the tissue deformation and reduced cell
volume,
suggesting that over-reduction of cell volume compromises
cell viability under this form of loading.
Finally, as
hypothesized, we found that cell death/injury after extreme loading
was significantly
affected by gender, age, load magnitude, load
duration and impact injury. Collectively, the findings
of this
study provide an advanced understanding of the factors that govern
the vulnerability of
articular chondrocytes to extreme loading
conditions, as well as insight into how to avoid
chondrocyte death
through…
Subjects/Keywords: Cartilage; Cell volume; Cell vulnerability; Chondrocyte; Impact; Sub-impact
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kotelsky, A. (2020). Elucidating the factors that govern vulnerability of in
situ articular chondrocytes to mechanical loading. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/35670
Chicago Manual of Style (16th Edition):
Kotelsky, Alexander. “Elucidating the factors that govern vulnerability of in
situ articular chondrocytes to mechanical loading.” 2020. Doctoral Dissertation, University of Rochester. Accessed April 13, 2021.
http://hdl.handle.net/1802/35670.
MLA Handbook (7th Edition):
Kotelsky, Alexander. “Elucidating the factors that govern vulnerability of in
situ articular chondrocytes to mechanical loading.” 2020. Web. 13 Apr 2021.
Vancouver:
Kotelsky A. Elucidating the factors that govern vulnerability of in
situ articular chondrocytes to mechanical loading. [Internet] [Doctoral dissertation]. University of Rochester; 2020. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1802/35670.
Council of Science Editors:
Kotelsky A. Elucidating the factors that govern vulnerability of in
situ articular chondrocytes to mechanical loading. [Doctoral Dissertation]. University of Rochester; 2020. Available from: http://hdl.handle.net/1802/35670
University of Rochester
30.
Catheline, Sarah Elizabeth.
Inflammation in Osteoarthritis Pathogenesis: Contribution
of IKKβ/NF-κB Signaling and Interplay with Chondrocyte
Hypertrophy.
Degree: PhD, 2020, University of Rochester
URL: http://hdl.handle.net/1802/35815
► Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation that affects all tissues within the synovial joint. OA is associated with an…
(more)
▼ Osteoarthritis (OA) is a degenerative joint disease
characterized by articular cartilage degradation that affects all
tissues within the synovial joint. OA is associated with an
enormous public health burden, as it is the most common cause of
disability in the United States. Two critical risk factors for
development of OA are advanced age and prior traumatic joint
injury. Age-associated chronic, low-grade inflammation is now
recognized as a likely contributor to disease, as are both the
acute and chronic phases of inflammation experienced by the joint
following traumatic injury. We have characterized the
age-associated spontaneous development of OA in a C57BL/6J mouse
model and both male and female mice develop a joint phenotype
consistent with early-stage OA; this includes proteoglycan staining
loss within the articular cartilage extracellular matrix (ECM),
synovial hyperplasia and immune cell infiltration, and an increase
in the overall size and mineralized area of the meniscus. Using a
transcriptomics approach, we see that aged articular cartilage has
increased expression of factors that act as positive regulators of
IKKβ/NF-κB signaling relative to younger articular cartilage, and
that several factors involved in the DNA damage response are also
upregulated. Similarly, upregulation of inflammatory factors
regulated by NF-κB signaling, such as TNF-α and CCL20, is seen in
various tissues within the knee joint following administration of a
meniscal-ligamentous injury (MLI). Based on this collective set of
data, we make the central hypothesis that inflammation driven by
activation of canonical NF-κB signaling functions as an initiating
event in the pathogenesis of OA, and that activation of the pathway
in a cartilage-specific manner using a genetic approach in young,
uninjured joints could accelerate onset and progression of OA. To
test this hypothesis, we generated postnatal chondrocyte-specific
IKKβ gain-of-function (GOF) mice. Remarkably, IKKβ GOF mice develop
a phenotype strikingly similar to the age-associated joint
pathology seen in wild C57BL/6J mice, but it develops at a largely
accelerated rate, suggesting that IKKβ GOF enhances spontaneous OA
development. These IKKβ GOF chondrocytes are capable of
upregulating markers of cellular senescence and negative regulators
of apoptosis, and can produce a senescence-associated secretory
phenotype (SASP) in vitro. Using this model, we have identified
CCL20 as a highly upregulated downstream target of IKKβ in
chondrocytes that may play a critical role in recruitment and
activation of immune cells to the knee joint during the process of
aging and following joint traumatic injury. Strikingly, initial
experiments performing meniscal-ligamentous injury on knockout
animals for the receptor for CCL20, CCR6, reveal that CCR6 knockout
mice are protected from joint degeneration following traumatic knee
injury.
In experiments parallel to these, we examined the
ability of inflammation induced by traumatic injury to regulate the
process of chondrocyte hypertrophy during OA…
Subjects/Keywords: Aging; Cartilage; Chondrocyte; IKKβ; NF-κB signaling; Osteoarthritis
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Catheline, S. E. (2020). Inflammation in Osteoarthritis Pathogenesis: Contribution
of IKKβ/NF-κB Signaling and Interplay with Chondrocyte
Hypertrophy. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/35815
Chicago Manual of Style (16th Edition):
Catheline, Sarah Elizabeth. “Inflammation in Osteoarthritis Pathogenesis: Contribution
of IKKβ/NF-κB Signaling and Interplay with Chondrocyte
Hypertrophy.” 2020. Doctoral Dissertation, University of Rochester. Accessed April 13, 2021.
http://hdl.handle.net/1802/35815.
MLA Handbook (7th Edition):
Catheline, Sarah Elizabeth. “Inflammation in Osteoarthritis Pathogenesis: Contribution
of IKKβ/NF-κB Signaling and Interplay with Chondrocyte
Hypertrophy.” 2020. Web. 13 Apr 2021.
Vancouver:
Catheline SE. Inflammation in Osteoarthritis Pathogenesis: Contribution
of IKKβ/NF-κB Signaling and Interplay with Chondrocyte
Hypertrophy. [Internet] [Doctoral dissertation]. University of Rochester; 2020. [cited 2021 Apr 13].
Available from: http://hdl.handle.net/1802/35815.
Council of Science Editors:
Catheline SE. Inflammation in Osteoarthritis Pathogenesis: Contribution
of IKKβ/NF-κB Signaling and Interplay with Chondrocyte
Hypertrophy. [Doctoral Dissertation]. University of Rochester; 2020. Available from: http://hdl.handle.net/1802/35815
◁ [1] [2] [3] [4] [5] [6] ▶
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Open Access Theses and Dissertations