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1.
Leslie, Shirae.
The controlled release of rat adipose-derived stem cells from alginate microbeads for bone regeneration.
Degree: MS, Biomedical Engineering (Joint GT/Emory Department), 2013, Georgia Tech
URL: http://hdl.handle.net/1853/48946 
► Cell-based therapies have potential for tissue regeneration but poor delivery methods lead to low viability or dispersal of cells from target sites, limiting clinical utility.…
(more)
▼ Cell-based therapies have potential for tissue regeneration but poor delivery methods lead to low viability or dispersal of cells from target sites, limiting clinical utility. Here, we developed a degradable and injectable hydrogel to deliver stem cells for bone regeneration. Alginate microbeads <200µm are injectable, persist at implantation sites and contain viable cells, but do not readily degrade in-vivo. We hypothesized that controlled release of rat adipose-derived stem cells (ASCs) from alginate microbeads can be achieved by incorporating alginate-lyase in the hydrogel. Microbeads were formed using high electrostatic potential. Controlled degradation was achieved through direct combination of alginate-lyase and alginate at 4°C. Results showed that microbead degradation and cell release depended on the alginate-lyase to alginate ratio. Viability of released cells ranged from 87% on day 2 to 71% on day 12. Monolayer cultures of released ASCs grown in osteogenic medium produced higher levels of osteocalcin and similar levels of other soluble factors as ASCs that were neither previously encapsulated nor exposed to alginate-lyase. Bmp2, Fgf2, and Vegfa mRNA in released cells were also increased. Thus, this delivery system allows for controlled release of viable cells and can modulate their downstream osteogenic factor production.
Advisors/Committee Members: Boyan, Barbara (advisor), Schwartz, Zvi (committee member), Mcdevitt, Todd (committee member), Tsukruk, Vladimir (committee member).
Subjects/Keywords: Cell encapsulation; Alginate degradation; Hydrogel; Stem cells; Bone regeneration; Fractures Treatment; Cellular therapy
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APA (6th Edition):
Leslie, S. (2013). The controlled release of rat adipose-derived stem cells from alginate microbeads for bone regeneration. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/48946
Chicago Manual of Style (16th Edition):
Leslie, Shirae. “The controlled release of rat adipose-derived stem cells from alginate microbeads for bone regeneration.” 2013. Masters Thesis, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/48946.
MLA Handbook (7th Edition):
Leslie, Shirae. “The controlled release of rat adipose-derived stem cells from alginate microbeads for bone regeneration.” 2013. Web. 17 Apr 2021.
Vancouver:
Leslie S. The controlled release of rat adipose-derived stem cells from alginate microbeads for bone regeneration. [Internet] [Masters thesis]. Georgia Tech; 2013. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/48946.
Council of Science Editors:
Leslie S. The controlled release of rat adipose-derived stem cells from alginate microbeads for bone regeneration. [Masters Thesis]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/48946
2.
Myers, Meredith A.
Development of a method for correlating integrin beta 1 expression and surface characteristics under individual cells.
Degree: MS, Materials Science and Engineering, 2011, Georgia Tech
URL: http://hdl.handle.net/1853/42718
► Osseointegration, or the direct integration of an implant into bone tissue, is necessary for implant success. Titanium is commonly used clinically in dental and orthopaedic…
(more)
▼ Osseointegration, or the direct integration of an implant into bone tissue, is necessary for implant success. Titanium is commonly used clinically in dental and orthopaedic implants because of its passivating oxide layer, which facilitates osseointegration, and its mechanical properties such as a modulus of elasticity similar to bone. Diverse studies have shown that surface microtopography, chemistry, and surface energy affect osteoblast behavior. The problem with these studies is that they access the average behavior of a culture in response to a substrate and not the behavior of individual cells. The objective of this study was to develop a method for correlating the behavior of individual cells with the characteristics of the surface underneath them. More specifically, this work developed a method to correlate integrin beta-1 (β1) expression with the surface characteristics under individual cells. Integrins are cell surface receptors that bind to specific proteins in the extracellular matrix adsorbed on the implant surface. Previous work has shown that expression of certain integrins is increased when osteoblasts on titanium substrates develop a more differentiated phenotype, and that integrin β1 is necessary for osteoblast response to roughness on titanium substrates.
This study used molecular beacons specific to integrin β1 to quantify integrin β1 expression of MG63 cells cultured on titanium disks. A template was designed to coordinate the location of cells using fluorescence microscopy and scanning electron microscopy (SEM) in reference to laser etchings on the disks. After live cell imaging, cells were fixed, dried, and critical point dried for focused ion beam (FIB) milling. Transmission electron microscopy (TEM) sections of cells identified with high and low integrin β1 molecular beacon intensity were milled, and cells with high and low integrin β1 molecular beacon intensity were also serial sectioned. While our TEM results were inconclusive, SEM images from serial sectioning showed contact points between the cell body and the substrate, consistent with previous results. Cells cultured on pretreatment (PT) or sandblasted acid etched (SLA) titanium surfaces were also serial sectioned, showing that cells on SLA surfaces have more regions of contact between the cells and the substrate than cells on PT surfaces.
This work is significant as it is the first study to develop a method to correlate individual cell behavior with the substrate surface characteristics under the individual cells. Previous studies have reported the average cell behavior in response to their substrates, while this work allows for the study of substrate surface characteristics that positively affect integrin β1 expression in individual cells. Further optimization of the fluorescence imaging process and FIB milling process could be done, and the method developed in this study could be used in future studies to investigate surface characteristics after using other fluorescent analyses of cell behavior, such as…
Advisors/Committee Members: Boyan, Barbara D. (Committee Chair), Sandhage, Ken (Committee Member), Schwartz, Zvi (Committee Member).
Subjects/Keywords: Titanium implants; Integrins; Molecular beacons; Focused ion beam (FIB) milling; Integrins; Osseointegration; Orthopedic implants; Cell adhesion
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APA (6th Edition):
Myers, M. A. (2011). Development of a method for correlating integrin beta 1 expression and surface characteristics under individual cells. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/42718
Chicago Manual of Style (16th Edition):
Myers, Meredith A. “Development of a method for correlating integrin beta 1 expression and surface characteristics under individual cells.” 2011. Masters Thesis, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/42718.
MLA Handbook (7th Edition):
Myers, Meredith A. “Development of a method for correlating integrin beta 1 expression and surface characteristics under individual cells.” 2011. Web. 17 Apr 2021.
Vancouver:
Myers MA. Development of a method for correlating integrin beta 1 expression and surface characteristics under individual cells. [Internet] [Masters thesis]. Georgia Tech; 2011. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/42718.
Council of Science Editors:
Myers MA. Development of a method for correlating integrin beta 1 expression and surface characteristics under individual cells. [Masters Thesis]. Georgia Tech; 2011. Available from: http://hdl.handle.net/1853/42718
3.
Fang, Mimi.
The role of phospholipase d in osteoblasts in response to titanium surfaces.
Degree: MS, Biomedical Engineering, 2008, Georgia Tech
URL: http://hdl.handle.net/1853/26462
► Biomaterial surface properties such as microtopography and energy can change cellular responses at the cell-implant interface. Phospholipase D (PLD) is required for differentiation of osteoblast-like…
(more)
▼ Biomaterial surface properties such as microtopography and energy can change cellular responses at the cell-implant interface. Phospholipase D (PLD) is required for differentiation of osteoblast-like MG63 cells on machined and grit-blasted titanium surfaces. Here, we determined if PLD is also required on microstructured/high-energy substrates and the mechanism involved. shRNAs for human PLD1 and PLD2 were used to silence MG63 cells. Wild-type and PLD1 or PLD1/2 silenced cells were cultured on smooth-pretreatment surfaces (PT); grit-blasted, acid-etched surfaces (SLA); and SLA surfaces modified to have higher surface energy (modSLA). PLD was inhibited with ethanol or activated with 24,25-dihydroxyvitamin-D₃ [24R,25(OH)₂D₃]. As surface roughness/energy increased, PLD mRNA and activity increased, cell number decreased, osteocalcin and osteoprotegerin increased, and protein kinase C (PKC) and alkaline phosphatase specific activities increased. Ethanol inhibited PLD and reduced surface effects on these parameters. There was no effect on these parameters after knockdown of PLD1, but PLD1/2 double knockdown had effects comparable to PLD inhibition. 24R,25(OH)₂D₃increased PLD activity and production of osteocalcin and osteoprotegerin, but decreased cell number on the rough/high-energy surfaces. These results confirm that surface roughness/energy-induced PLD activity is required for osteoblast differentiation and that PLD2 is the main isoform involved in this pathway. Here we showed that PLD is activated by 24R,25(OH)₂D₃ in a surface-dependent manner and inhibition of PLD reduced the effects of surface microstructure/energy on PKC, suggesting that PLD mediates the stimulatory effect of microstructured/high-energy surfaces via PKC-dependent signaling.
Advisors/Committee Members: Boyan, Barbara (Committee Chair), Eskin, Suzanne (Committee Member), Lobachev, Kirill (Committee Member), Schwartz, Zvi (Committee Member).
Subjects/Keywords: Osteoblasts; Phospholipase D; Titanium implants; Surface energy; Biomedical materials; Surface roughness; Implants, Artificial Physiological effect; Phospholipases
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APA (6th Edition):
Fang, M. (2008). The role of phospholipase d in osteoblasts in response to titanium surfaces. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/26462
Chicago Manual of Style (16th Edition):
Fang, Mimi. “The role of phospholipase d in osteoblasts in response to titanium surfaces.” 2008. Masters Thesis, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/26462.
MLA Handbook (7th Edition):
Fang, Mimi. “The role of phospholipase d in osteoblasts in response to titanium surfaces.” 2008. Web. 17 Apr 2021.
Vancouver:
Fang M. The role of phospholipase d in osteoblasts in response to titanium surfaces. [Internet] [Masters thesis]. Georgia Tech; 2008. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/26462.
Council of Science Editors:
Fang M. The role of phospholipase d in osteoblasts in response to titanium surfaces. [Masters Thesis]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/26462
Georgia Tech
4.
Doroudi, Maryam.
Essential roles of Pdia3/PLAA receptor complex and CaMKII IN 1α,25(OH)₂D₃ and Wnt5a calcium-dependent signaling pathways in osteoblasts and chondrocytes.
Degree: PhD, Biology, 2014, Georgia Tech
URL: http://hdl.handle.net/1853/53427
► The vitamin D metabolite 1,25-dihydroxyvitamin D3 [1α,25(OH)2D3] plays an important role in the regulation of musculoskeletal growth and differentiation. 1α,25(OH)2D3 mediates its effects on cells,…
(more)
▼ The vitamin D metabolite 1,25-dihydroxyvitamin D3 [1α,25(OH)2D3] plays an important role in the regulation of musculoskeletal growth and differentiation. 1α,25(OH)2D3 mediates its effects on cells, including chondrocytes and osteoblasts, through the classical nuclear 1α,25(OH)2D3 receptor. Additionally, recent evidence indicates that several cellular responses to 1α,25(OH)2D3 are mediated via a rapid, calcium-dependent membrane-mediated pathway. These actions of 1α,25(OH)2D3 can be blocked by antibodies to protein-disulfide isomerase family A, member 3 (Pdia3), indicating that it is part of the receptor complex; however, the pathway which is activated by this receptor is not fully understood. The overall goal of this thesis was to examine the roles of phospholipase A2 activating protein (PLAA) and calcium calmodulin-dependent kinase II (CaMKII) in 1α,25(OH)2D3 rapid membrane-mediated signaling. We further investigated the interaction between two pathways regulating growth plate cartilage and endochondral bone formation, 1α,25(OH)2D3 and Wnt5a, at the receptor complex level. Results indicated that PLAA was required for mediating 1α,25(OH)2D3 signal from Pdia3. Furthermore, CaM and CaMKII were identified as mediators of 1α,25(OH)2D3-stimulated PLAA-dependent activation of cPLA2 and PKCα, and downstream biological effects. Wnt5a and 1α,25(OH)2D3 are important regulators of endochondral bone formation. This study demonstrated that 1α,25(OH)2D3 and Wnt5a mediate their effects via similar receptor components in osteoblasts and chondrocytes suggesting that these pathways may interact.
Advisors/Committee Members: Boyan, Barbara D. (advisor), Shin, Chong (committee member), Jo, Hanjoong (committee member), Merrill, Al (committee member), Schwartz, Zvi (committee member), Ziegler, Thomas (committee member).
Subjects/Keywords: 1,25-dihydroxyvitamin D3; Growth plate
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APA (6th Edition):
Doroudi, M. (2014). Essential roles of Pdia3/PLAA receptor complex and CaMKII IN 1α,25(OH)₂D₃ and Wnt5a calcium-dependent signaling pathways in osteoblasts and chondrocytes. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/53427
Chicago Manual of Style (16th Edition):
Doroudi, Maryam. “Essential roles of Pdia3/PLAA receptor complex and CaMKII IN 1α,25(OH)₂D₃ and Wnt5a calcium-dependent signaling pathways in osteoblasts and chondrocytes.” 2014. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/53427.
MLA Handbook (7th Edition):
Doroudi, Maryam. “Essential roles of Pdia3/PLAA receptor complex and CaMKII IN 1α,25(OH)₂D₃ and Wnt5a calcium-dependent signaling pathways in osteoblasts and chondrocytes.” 2014. Web. 17 Apr 2021.
Vancouver:
Doroudi M. Essential roles of Pdia3/PLAA receptor complex and CaMKII IN 1α,25(OH)₂D₃ and Wnt5a calcium-dependent signaling pathways in osteoblasts and chondrocytes. [Internet] [Doctoral dissertation]. Georgia Tech; 2014. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/53427.
Council of Science Editors:
Doroudi M. Essential roles of Pdia3/PLAA receptor complex and CaMKII IN 1α,25(OH)₂D₃ and Wnt5a calcium-dependent signaling pathways in osteoblasts and chondrocytes. [Doctoral Dissertation]. Georgia Tech; 2014. Available from: http://hdl.handle.net/1853/53427
Georgia Tech
5.
Sutha, Ken.
Osteoinductive material derived from differentiating embryonic stem cells.
Degree: PhD, Biomedical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/51722
► The loss of regenerative capacity of bone, from fetal to adult to aged animals, has been attributed not only to a decline in the function…
(more)
▼ The loss of regenerative capacity of bone, from fetal to adult to aged animals, has been attributed not only to a decline in the function of cells involved in bone formation but also to alterations in the bone microenvironment that occur through development and aging, including extracellular matrix (ECM) composition and growth/trophic factor content. In the development of novel treatments for bone repair, one potential therapeutic goal is the restoration of a more regenerative microenvironment, as found during embryonic development. One approach to creating such a microenvironment is through the use of stem cells. In addition to serving as a differentiated cell source, pluripotent stem cells, such as embryonic stem cells (ESCs), may possess the unique potential to modulate tissue environments via local production of ECM and growth factors. ESC-produced factors may be harnessed and delivered to promote functional tissue regeneration. Such an approach to generate a naturally derived, acelluar therapy has been employed successfully to deliver osteoinductive factors found within adult bone, in the form of demineralized bone matrix (DBM), but the development of treatments derived instead from developing, more regenerative tissues or cells remains attractive. Furthermore, the derivation of regenerative materials from an ESC source also presents the added benefit of eliminating donor to donor variability of adult, cadaveric tissue derived materials, such as DBM. Thus, the objective of this project was to examine the osteoinductive potential harbored within the embryonic microenvironment, in vitro and in vivo. The osteogenic differentiation of mouse ESCs as embryoid bodies (EBs) was evaluated in response to phosphate treatment, in vitro, including osteoinductive growth factor production. The osteoinductivity of EB-derived material (EBM) was then compared to that of adult tissue-derived DBM, in vivo. Phosphate treatment enhanced osteogenic differentiation of EBs. EBM derived from phosphate treated EBs retained bioactive, osteoinductive factors and induced new bone formation, demonstrating that the microenvironment within osteogenic EBs can be harnessed in an acellular material to yield in vivo osteoinductivity. This work not only provides new insights into the dynamic microenvironments of differentiating stem cells but also establishes an approach for the development of an ESC-derived, tissue specific therapy.
Advisors/Committee Members: McDevitt, Todd C. (advisor), Guldberg, Robert E. (committee member), Schwartz, Zvi (committee member), Boyan, Barbara D. (committee member), O'Connell, Julie (committee member), Temenoff, Johanna S. (committee member).
Subjects/Keywords: Regenerative medicine; Regenerative therapy; Bone therapy; Embryonic stem cells; Embryonic stem cells; Bone regeneration
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APA (6th Edition):
Sutha, K. (2012). Osteoinductive material derived from differentiating embryonic stem cells. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/51722
Chicago Manual of Style (16th Edition):
Sutha, Ken. “Osteoinductive material derived from differentiating embryonic stem cells.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/51722.
MLA Handbook (7th Edition):
Sutha, Ken. “Osteoinductive material derived from differentiating embryonic stem cells.” 2012. Web. 17 Apr 2021.
Vancouver:
Sutha K. Osteoinductive material derived from differentiating embryonic stem cells. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/51722.
Council of Science Editors:
Sutha K. Osteoinductive material derived from differentiating embryonic stem cells. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/51722
Georgia Tech
6.
Cheng, Alice.
Multi-scale structural design of titanium implants for improved osseointegration.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2016, Georgia Tech
URL: http://hdl.handle.net/1853/56287
► Osseointegration success of bone-interfacing implants is reduced for many compromised patients, necessitating improved implant design. Though material and mechanical properties of titanium make it attractive…
(more)
▼ Osseointegration success of bone-interfacing implants is reduced for many compromised patients, necessitating improved implant design. Though material and mechanical properties of titanium make it attractive for load-bearing dental and orthopaedic implants, limited advancements have been made to increase success and survival after placement in the body. Novel surface modifications inducing combined micro- and nano-roughness on Ti and Ti-6Al-4V substrates contribute to increased wettability and can be tailored to affect cell response. Additive manufacturing can produce three dimensional constructs with natural, trabeculae-inspired porosity. Osteoblasts and mesenchymal stem cells are responsive to the porosity and detail of these constructs, and exhibit increased production of osteoblastic differentiation and maturation factors on porous constructs compared to solid substrates. Implants with trabecular porosity lead to vertical bone growth on rat calvaria, and osseointegrate in the rabbit femur. These results indicate that structural micro- and nano-modification at the surface, combined with macro-scale porosity, can enhance osteoblastic differentiation and maturation in vitro, and osseointegration in vivo. These implants are now being evaluated in clinical studies.
Advisors/Committee Members: Boyan, Barbara D (advisor), Zhu, Cheng (advisor), Schwartz, Zvi (committee member), Chen, Haifeng (committee member), Roy, Krishnendu (committee member), Sandhage, Kenneth H (committee member).
Subjects/Keywords: biomaterials; osseointegration, osteoblast differentiation; titanium; additive manufacturing
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APA (6th Edition):
Cheng, A. (2016). Multi-scale structural design of titanium implants for improved osseointegration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/56287
Chicago Manual of Style (16th Edition):
Cheng, Alice. “Multi-scale structural design of titanium implants for improved osseointegration.” 2016. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/56287.
MLA Handbook (7th Edition):
Cheng, Alice. “Multi-scale structural design of titanium implants for improved osseointegration.” 2016. Web. 17 Apr 2021.
Vancouver:
Cheng A. Multi-scale structural design of titanium implants for improved osseointegration. [Internet] [Doctoral dissertation]. Georgia Tech; 2016. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/56287.
Council of Science Editors:
Cheng A. Multi-scale structural design of titanium implants for improved osseointegration. [Doctoral Dissertation]. Georgia Tech; 2016. Available from: http://hdl.handle.net/1853/56287
7.
Hyzy, Sharon Leigh.
Adverse effects of bone morphogenic protein-2 during osseointegration.
Degree: MS, Biology, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/44728
► Modifications of biomaterial surface properties are employed to increase osteoblast differentiation and bone formation. Microtextured metallic surfaces promote osteoblast differentiation and high surface energy- achieved…
(more)
▼ Modifications of biomaterial surface properties are employed to increase osteoblast differentiation and bone formation. Microtextured metallic surfaces promote osteoblast differentiation and high surface energy- achieved by controlling surface hydrocarbon contamination- increases osteoblast differentiation and peri-implant bone formation. Recombinant human bone morphogenic protein 2 (BMP2) is approved to induce bone formation in a number of applications. It is used clinically in combination with biomaterials to improve peri-implant bone formation and osseointegration. The amount of BMP2 that is required is large and inflammatory (swelling/seroma) and bone-related (ectopic bone/bone resorption) complications have been reported after BMP2 treatment. The aim of this study was to examine potential deleterious effects of BMP2 on the inflammatory environment and apoptosis of osteoblasts.
Surface roughness and energy decreased pro-inflammatory interleukins and increased anti-inflammatory interleukins. In contrast, BMP2 abolished the surface effect, increasing pro-inflammatory interleukin (IL) 6, IL8, and IL17 in a surface roughness-dependent fashion and decreasing anti-inflammatory IL10 on rough surfaces. 5Z-7-Oxozeaenol and Dorsomorphin, but not H-8, blocked the effect of BMP2 on IL1A expression. There was an increase in expression of IL6 when treated with BMP2 for the control and H-8 groups, but both 5Z-7-Oxozeaenol and Dorsomorphin blocked the effect. Both 5Z-7-Oxozeaenol and H-8 blocked the effect of BMP2 on IL10 expression.
BMP2 treatment had little effect on apoptosis in human mesenchymal stem cells (MSCs). Exogenous BMP2 had no effect on TUNEL. Caspase-3 activity was increased only at 200ng/ml BMP2. BAX/BCL2 decreased in MSCs treated with 50 and 100ng/ml BMP2. In contrast, BMP2 increased caspase-3 activity and TUNEL at all doses in normal human osteoblasts (NHOst). BAX/BCL2 increased in NHOst treated with BMP2 in a dose-dependent manner. Cells treated with 200 ng/ml BMP2 had an 8-fold increase in BAX/BCL2 expression in comparison with untreated cells. Similarly, BMP2 increased DNA fragmentation in NHOst cells. The BMP2-induced increase in DNA fragmentation was eliminated by 5-Z7-Oxozeaenol and Dorsomorphin.
The results suggest that while surface features modulate an initial controlled inflammatory response, the addition of BMP2 induces a pro-inflammatory response. The effect of BMP2 on apoptosis depends on cell maturation state, inducing apoptosis in committed osteoblasts. BMP2 together with microtextured orthopaedic and dental implants may increase inflammation and possibly delay bone formation. Dose, location, and delivery strategies are important considerations in BMP2 as a therapeutic and must be optimized to minimize complications.
Advisors/Committee Members: Boyan, Barbara D. (Committee Chair), Schwartz, Zvi (Committee Co-Chair), Lobachev, Kirill (Committee Member), Streelman, J. Todd (Committee Member).
Subjects/Keywords: Osteoblasts; Apoptosis; Titanium; Microstructure; Osseointegration; Inflammation; Interleukins; Guided bone regeneration; Bone morphogenetic proteins; Growth factors
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APA ·
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APA (6th Edition):
Hyzy, S. L. (2012). Adverse effects of bone morphogenic protein-2 during osseointegration. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44728
Chicago Manual of Style (16th Edition):
Hyzy, Sharon Leigh. “Adverse effects of bone morphogenic protein-2 during osseointegration.” 2012. Masters Thesis, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/44728.
MLA Handbook (7th Edition):
Hyzy, Sharon Leigh. “Adverse effects of bone morphogenic protein-2 during osseointegration.” 2012. Web. 17 Apr 2021.
Vancouver:
Hyzy SL. Adverse effects of bone morphogenic protein-2 during osseointegration. [Internet] [Masters thesis]. Georgia Tech; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/44728.
Council of Science Editors:
Hyzy SL. Adverse effects of bone morphogenic protein-2 during osseointegration. [Masters Thesis]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/44728
8.
Pan, Qingfen.
Qingfen_Pan_Dissertation.
Degree: PhD, Mechanical Engineering, 2015, Georgia Tech
URL: http://hdl.handle.net/1853/54873
► Osteoarthritis (OA) is a degenerative disease characterized by joint inflammation and cartilage degeneration due to matrix degradation and chondrocyte apoptosis. Previously, drug therapies have been…
(more)
▼ Osteoarthritis (OA) is a degenerative disease characterized by joint inflammation and cartilage degeneration due to matrix degradation and chondrocyte apoptosis. Previously, drug therapies have been developed that aim to ease pain and reduce local inflammation. Currently, no effective drug exists that has no significant side effects. Therefore, an unmet medical demand exists for development of tissue-engineering strategies to promote articular cartilage repair and regeneration to treat OA. 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] is an attractive option for articular cartilage repair because of its anti-inflammatory and anti-apoptotic properties. 24R,25(OH)2D3, which is a naturally occurring metabolite of vitamin D3, also has not been shown to cause toxic side effects. Results from the study demonstrate that 24R,25(OH)2D3 can inhibit chondrocyte apoptosis and suppress the production of catabolic factors that result in cartilage degeneration in the in vitro model. Furthermore, although 24R,25(OH)2D3 regulates components of TGF-β1 pathway, the effect of 24R,25(OH)2D3 is not mediated through TGF-β1 signaling. In vivo delivery of 24R,25(OH)2D3 prevented cartilage degeneration and disease progression. In addition, intraarticular injection of 24R,25(OH)2D3 had an effect on cytokines and growth factors production both locally and systemically. Human articular chondrocytes responded to 24R,25(OH)2D3 treatment in both sex and maturation dependent manner. Collectively, results from this study suggest that 24R,25(OH)2D3 ccould be used as a clinical therapy for knee OA.
Advisors/Committee Members: Boyan, Barbara (advisor), Schwartz, Zvi (committee member), Babensee, Julia (committee member), Platt, Manu (committee member), Dixon, Brandon (committee member).
Subjects/Keywords: Osteoarthritis; 24R; 25(OH)2D3
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APA (6th Edition):
Pan, Q. (2015). Qingfen_Pan_Dissertation. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/54873
Chicago Manual of Style (16th Edition):
Pan, Qingfen. “Qingfen_Pan_Dissertation.” 2015. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/54873.
MLA Handbook (7th Edition):
Pan, Qingfen. “Qingfen_Pan_Dissertation.” 2015. Web. 17 Apr 2021.
Vancouver:
Pan Q. Qingfen_Pan_Dissertation. [Internet] [Doctoral dissertation]. Georgia Tech; 2015. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/54873.
Council of Science Editors:
Pan Q. Qingfen_Pan_Dissertation. [Doctoral Dissertation]. Georgia Tech; 2015. Available from: http://hdl.handle.net/1853/54873
9.
Zhong, Ming.
Apoptotic signaling pathways in mammalian growth plate chondrocytes.
Degree: PhD, Biomedical Engineering, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/33993
► The growth plate resting zone consists of hyaline-like chondrocytes disbursed in a proteoglycan rich extracellular matrix. These cells give rise to the columns of the…
(more)
▼ The growth plate resting zone consists of hyaline-like chondrocytes disbursed in a proteoglycan rich extracellular matrix. These cells give rise to the columns of the growth zone, consisting of progressively hypertrophic cells. Proliferation of resting zone chondrocytes induced by systemic and local stimuli is the driving force of longitudinal growth of long bones. Therefore, homeostasis of this cell population has great importance. Although the regulation of proliferation and differentiation of these cells has been well studied, little is known about the regulation of their apoptosis. We have previously shown that chelerythrine and tamoxifen induce apoptosis in resting zone chondrocytes in a nitric oxide (NO)-dependent pathway. In this study we explored two physiological apoptogens: inorganic phosphate (Pi) and 17β-estradiol (E₂). We found NO production is necessary in Pi-induced apoptosis. We also found that NO donors induced chondrocyte apoptosis by up-regulating p53 expression, Bax/Bcl-2 expression ratio and cytochrome C release from mitochondria, as well as caspase-3 activity, indicating that NO induces chondrocyte apoptosis in a mitochondrial pathway. Mitogen activated protein kinase (MAPK) activity was involved. A c-Jun N-terminal kinase (JNK) inhibitor, but not inhibitors of p38 or extracellular signal-regulated kinase (ERK1/2), was able to block NO-induced apoptosis, indicating that JNK is necessary in this pathway. Taken together, Pi elevates NO production, which leads to a mitochondrial apoptotic pathway dependent on JNK. On the other hand, although E₂caused apoptosis in resting zone chondrocytes in a dose-dependent manner, up-regulated p53 and Bax, and induced release of cytochrome C from the mitochondria, which indicated a mitochondrial apoptotic pathway, the apoptosis did not involve elevated nitric oxide production or MAPK as was found in Pi-induced apoptosis. This study elucidates the signaling pathway underlying Pi and E₂-induced chondrocyte apoptosis. It has important implications on understanding the development of mammalian growth plate. It also provides further information about the physiological functions of estrogen on longitudinal bone growth.
Advisors/Committee Members: Boyan, Barbara (Committee Chair), Carney, Darrell (Committee Member), Jo, Hanjoong (Committee Member), Lobachev, Kirill (Committee Member), Schwartz, Zvi (Committee Member).
Subjects/Keywords: Apoptosis; MAP kinases; Nitric oxide; Phosphates; P53; Estrogen; Growth plate chondrocytes; Endochondral ossification; Growth plate; Bones Growth; Cartilage; Bone; Ossification
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APA (6th Edition):
Zhong, M. (2010). Apoptotic signaling pathways in mammalian growth plate chondrocytes. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/33993
Chicago Manual of Style (16th Edition):
Zhong, Ming. “Apoptotic signaling pathways in mammalian growth plate chondrocytes.” 2010. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/33993.
MLA Handbook (7th Edition):
Zhong, Ming. “Apoptotic signaling pathways in mammalian growth plate chondrocytes.” 2010. Web. 17 Apr 2021.
Vancouver:
Zhong M. Apoptotic signaling pathways in mammalian growth plate chondrocytes. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/33993.
Council of Science Editors:
Zhong M. Apoptotic signaling pathways in mammalian growth plate chondrocytes. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/33993
10.
Kinney, Ramsey Christian.
The role of sexual dimorphism in cartilage tissue regeneration.
Degree: PhD, Biomedical Engineering, 2008, Georgia Tech
URL: http://hdl.handle.net/1853/28225
► Osteoarthritis is a degenerative joint disease characterized by progressive erosion of the articular cartilage. Epidemiological studies have established a relationship between osteoarthritis and menopause suggesting…
(more)
▼ Osteoarthritis is a degenerative joint disease characterized by progressive erosion of the articular cartilage. Epidemiological studies have established a relationship between osteoarthritis and menopause suggesting that estrogen may be important in the development of cartilage regeneration therapies. The overall goal of this research project was to advance the field of cartilage tissue regeneration by investigating the role of 17 ß -estradiol (E2), an active estrogen metabolite, on the chondrocyte phenotype. The central hypothesis was that E2 plays an important and sex-specific role in regulating chondrogenesis. Specific Aim-1 focused on establishing and characterizing a primary human articular chondrocyte (HAC) cell source, and then examining the response of the cells in culture to E2. It was demonstrated that the response of HACs to E2 treatment was sex-specific despite both male and females cells expressing estrogen receptors. Female HACs showed changes in proliferation, matrix production, and differentiation while male cells did not. In addition, the female response was regulated through a rapid membrane signaling pathway mediated by protein kinase C. Specific Aim-2 involved establishing an ovariectomized animal model to investigate the effects of E2 on orthopaedic tissue implants. Human demineralized bone matrix (DBM) was implanted intramuscularly into female nude mice and rats. Ovariectomy was shown to reduce the ability of DBM to induce the formation of cartilage and bone tissue. Moreover, the inductive properties of DBM were reestablished with subcutaneous E2 supplementation. Specific Aim-3 entailed developing and characterizing a microencapsulation method for in vitro culture and in vivo delivery of chondrocytes to study the effects of E2 on chondrogenesis. Rat growth plate chondrocytes and HACs were microencapsulated in alginate using an extrusion method in conjunction with high electrostatic potential. Chondrocytes maintained their phenotype in alginate suspension but were unable to form cartilage tissue when implanted into our animal model. Further optimization of the system is required before the role of E2 on chondrogenesis of tissue engineered constructs can be determined. In summary, our results suggest that the successful production of tissue engineered therapies will likely depend on understanding and manipulating the actions of sex hormones in both the in vitro and in vivo environment.
Advisors/Committee Members: Boyan, Barbara (Committee Chair), Bonassar, Lawrence (Committee Member), Sambanis, Anthanassios (Committee Member), Schwartz, Zvi (Committee Member), Wick, Timothy (Committee Member).
Subjects/Keywords: Estrogen; Chondrocyte; Tissue engineering; Sex-specific; Alginate; Electrostatic microencapsulation; Sexual dimorphism (Animals); Articular cartilage; Regeneration (Biology); Osteoarthritis; Estrogen
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APA (6th Edition):
Kinney, R. C. (2008). The role of sexual dimorphism in cartilage tissue regeneration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/28225
Chicago Manual of Style (16th Edition):
Kinney, Ramsey Christian. “The role of sexual dimorphism in cartilage tissue regeneration.” 2008. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/28225.
MLA Handbook (7th Edition):
Kinney, Ramsey Christian. “The role of sexual dimorphism in cartilage tissue regeneration.” 2008. Web. 17 Apr 2021.
Vancouver:
Kinney RC. The role of sexual dimorphism in cartilage tissue regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/28225.
Council of Science Editors:
Kinney RC. The role of sexual dimorphism in cartilage tissue regeneration. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/28225
11.
Chen, Jiaxuan.
The role of Pdia3 in vitamin D signaling in osteoblasts.
Degree: PhD, Biomedical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/50147
► 1a,25-Dihydroxyvitamin D3 (1a,25(OH)2D3) is a major functional metabolic form of vitamin D. 1a,25(OH)2D3 has drawn increasing attention due to its functions in addition to maintaining…
(more)
▼ 1a,25-Dihydroxyvitamin D3 (1a,25(OH)2D3) is a major functional metabolic form of vitamin D. 1a,25(OH)2D3 has drawn increasing attention due to its functions in addition to maintaining calcium phosphate homeostasis. It directly regulates mineralization by osteoblasts, matrix production and remodeling by chondrocytes, and contraction of cardiomyocytes. 1a,25(OH)2D3 and its analogues have shown beneficial effects in treating multiple sclerosis, diabetes and various types of cancer. In order to maximize the pharmaceutical potential of 1a,25(OH)2D3, a better understanding its cell signaling pathway is necessary. 1a,25(OH)2D3 regulates osteoblasts through both classical nuclear vitamin D receptor (nVDR) mediated genomic effects and plasma membrane receptor-mediated rapid responses. The identity of the plasma membrane receptor for 1a,25(OH)2D3 is controversial. Protein disulfide isomerase associated 3 (Pdia3) has been hypothesized as one of the putative plasma membrane receptors for 1a,25(OH)2D3. The overall goal of this thesis was to understand the general role and the molecular mechanism of Pdia3 in 1a,25(OH)2D3-initiated rapid responses, and to determine the role of Pdia3 and its dependent signaling in osteoblast biology. The results show that Pdia3 is required for membrane-mediated responses of 1a,25(OH)2D3. Moreover, both Pdia3 and nVDR are critical components of the plasma membrane receptor complex for 1a,25(OH)2D3. Finally, Pdia3 and signaling via Pdia3 regulate osteoblast differentiation and mineralization. Taken together, this study demonstrates the role of Pdia3 in rapid responses to 1a,25(OH)2D3 and osteoblast biology, reveals the unexpected complexity of the 1a,25(OH)2D3 plasma receptor complex and opens the new target, Pdia3, for pharmaceutical application and tissue engineering.
Advisors/Committee Members: Boyan, Barbara (advisor), Chen, Hong (committee member), Lobachev, Kirill (committee member), McDevitt, Todd (committee member), Schwartz, Zvi (committee member).
Subjects/Keywords: Rapid response; Osteoblasts; Vitamin D; VDR; Pdia3; Cholecalciferol; Cell receptors; Steroid hormones
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APA (6th Edition):
Chen, J. (2012). The role of Pdia3 in vitamin D signaling in osteoblasts. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/50147
Chicago Manual of Style (16th Edition):
Chen, Jiaxuan. “The role of Pdia3 in vitamin D signaling in osteoblasts.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/50147.
MLA Handbook (7th Edition):
Chen, Jiaxuan. “The role of Pdia3 in vitamin D signaling in osteoblasts.” 2012. Web. 17 Apr 2021.
Vancouver:
Chen J. The role of Pdia3 in vitamin D signaling in osteoblasts. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/50147.
Council of Science Editors:
Chen J. The role of Pdia3 in vitamin D signaling in osteoblasts. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/50147
12.
Gittens Ibacache, Rolando Arturo.
The role of nanostructural and electrical surface properties on the osteogenic potential of titanium implants.
Degree: PhD, Materials Science and Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/45800
► Dental and orthopaedic implants are currently the solutions of choice for teeth and joint replacements with success rates continually improving, but they still have undesirable…
(more)
▼ Dental and orthopaedic implants are currently the solutions of choice for teeth and joint replacements with success rates continually improving, but they still have undesirable failure rates in patients who are compromised by disease or age, and who in many cases are the ones most in need. The success of titanium (Ti) implants depends on their ability to osseointegrate with the surrounding bone and this, in turn, is greatly dependent on the surface characteristics of the device. Advancements in surface analysis and surface modification techniques have improved the biological performance of metallic implants by mimicking the hierarchical structure of bone associated with regular bone remodeling. In this process, damaged bone is resorbed by osteoclasts, which produce resorption lacunae containing high microroughness generated after mineral dissolution under the ruffled border, as well as superimposed nanoscale features created by the collagen fibers left at the surface. Indeed, increasing Ti surface roughness at the micro and sub-microscale level has been shown to increase osteoblast differentiation in vitro, increase bone-to-implant contact in vivo, and accelerate healing times clinically. Recently, the clinical application of surface nanomodification of implants has been evaluated. Still, most clinically-available devices remain smooth at the nanoscale and fundamental questions remain to be elucidated about the effect of nanoroughness on the initial response of osteoblast lineage cells.
Another property that could be used to control osteoblast development and the process of osseointegration is the electrical surface charge of implants. The presence of endogenous electrical signals in bone has been implicated in the processes of bone remodeling and repair. The existence of these native signals has prompted the use of external electrical stimulation to enhance bone growth in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports confirming its beneficial effects on bone formation. However, the use of electrical stimulation on Ti implants to enhance osseointegration is less understood, in part because of the lack of in vitro models that truly represent the in vivo environment. In addition, an aspect that has not been thoroughly examined is the electrical implication of implant corrosion and its effect on the surrounding tissue. Implants are exposed to extreme conditions in the body such as high pH during inflammation, and cyclic loads. These circumstances may lead to corrosion events that generate large electrochemical currents and potentials, and may cause abnormal cell and tissue responses that could be partly responsible for complications such as aseptic loosening of implants.
Consequently, Ti implants with tailored surface characteristics such as nanotopography and electrical polarization, could promote bone healing and osseointegration to ensure successful outcomes for patients by mimicking the biological environment of bone without the use of systemic drugs. The objective…
Advisors/Committee Members: Boyan, Barbara (Committee Chair), Tannenbaum, Rina (Committee Co-Chair), Butera, Robert (Committee Member), Sandhage, Kenneth (Committee Member), Schwartz, Zvi (Committee Member).
Subjects/Keywords: Electrical stimulation; Mesenchymal stem cells; Osteoblast differentiation; Surface nanomodification; Bone; Titanium implants; Surface preparation; Metals in medicine; Titanium; Osseointegration; Bone regeneration; Implants, Artificial; Orthopedic implants; Dental implants
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APA (6th Edition):
Gittens Ibacache, R. A. (2012). The role of nanostructural and electrical surface properties on the osteogenic potential of titanium implants. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45800
Chicago Manual of Style (16th Edition):
Gittens Ibacache, Rolando Arturo. “The role of nanostructural and electrical surface properties on the osteogenic potential of titanium implants.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/45800.
MLA Handbook (7th Edition):
Gittens Ibacache, Rolando Arturo. “The role of nanostructural and electrical surface properties on the osteogenic potential of titanium implants.” 2012. Web. 17 Apr 2021.
Vancouver:
Gittens Ibacache RA. The role of nanostructural and electrical surface properties on the osteogenic potential of titanium implants. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/45800.
Council of Science Editors:
Gittens Ibacache RA. The role of nanostructural and electrical surface properties on the osteogenic potential of titanium implants. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/45800
13.
ElBaradie, Khairat Bahgat.
Membrane effects of sex hormones on growth plate chondrocytes.
Degree: PhD, Biology, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/45956
► Understanding and studying the normal bone growth and development is causal. Bone and cartilage tissue provide in addition to their mechanical support, they provide a…
(more)
▼ Understanding and studying the normal bone growth and development is causal. Bone and cartilage tissue provide in addition to their mechanical support, they provide a protection for vital organs such as heart, lung and brain. Longitudinal growth is regulated by the activity of chondrocytes in the epiphyseal growth plates of long bones. Many hormones and growth factors are involved in the regulation of this process. Among these, sex steroids are of crucial importance, especially during puberty.
In long bones, endochondral bone formation occurs at the growth plate, a region of developing cartilage located between the epiphysis and the metaphysic. The process of endochondral ossification is regulated in part by sex steroid hormones. Androgens stimulate endochondral bone growth and elongation, while estrogen is known to suppress longitudinal bone growth and accelerate growth plate closure. Studies using rat costochondral growth plate chondrocytes as a model show that the effects of 17β-estradiol (E₂) on apoptosis are found in both male and female cells and the same mechanism is involved. In contrast, E₂ causes rapid activation of PKC in female cells but not in male cells. Dihydroxytestosterone (DHT) also has direct effects on growth plate chondrocytes, increasing matrix synthesis including sulfated glycosaminoglycan production, and enhancing cell maturation by increasing alkaline phosphatase enzymatic activity.
Short stature and abnormally slow increase in height is one of the main reasons for referral to endocrinologist. Excessive growth and abnormally tall is also a problem, especially because it increase risk for the trunk abnormalities. Furthermore until now a few growth-promoting therapies are available for clinical use. Therefore future therapies for treating the growth disorders are essential.
The overall goal of this project is to investigate the sexual-dimorphic effect of the sex steroid hormone in rat growth plate chondrocytes, the cellular signaling pathways mediating these actions, and their physiological role. The information gleaned from this study will provide new information about the role of sex steroid hormones in chondrogenesis and has implications in the development of new therapies for the treatment of bone fracture healing, and growth plate disorders. The central hypothesis was that sex steroid would play an important and sex-specific role in regulating chondrocytes as a main regulator of longitudinal bone growth.
Advisors/Committee Members: Barbarab, Boyan (Committee Chair), Schwartz, Zvi (Committee Co-Chair), Chernoff, Yury (Committee Member), Lobachev,Kirill (Committee Member), Wartell, Roger (Committee Member).
Subjects/Keywords: Estrogen receptor; Androgen receptor; Sex hormones; Hormones, Sex; Hormones, Sex Receptors; Androgens; Estrogen; Cartilage cells
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APA (6th Edition):
ElBaradie, K. B. (2012). Membrane effects of sex hormones on growth plate chondrocytes. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/45956
Chicago Manual of Style (16th Edition):
ElBaradie, Khairat Bahgat. “Membrane effects of sex hormones on growth plate chondrocytes.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/45956.
MLA Handbook (7th Edition):
ElBaradie, Khairat Bahgat. “Membrane effects of sex hormones on growth plate chondrocytes.” 2012. Web. 17 Apr 2021.
Vancouver:
ElBaradie KB. Membrane effects of sex hormones on growth plate chondrocytes. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/45956.
Council of Science Editors:
ElBaradie KB. Membrane effects of sex hormones on growth plate chondrocytes. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/45956
14.
Chaudhri, Reyhaan Ali.
The role of estrogen receptor-Alpha 36 in the membrane effect of 17Beta-estra.
Degree: PhD, Biology, 2013, Georgia Tech
URL: http://hdl.handle.net/1853/52162
► Breast cancer is a heterogeneous disease that afflicts all patients differently, and therefore requires individualized treatment depending on a large variety of factors. Several methods…
(more)
▼ Breast cancer is a heterogeneous disease that afflicts all patients differently, and therefore requires individualized treatment depending on a large variety of factors. Several methods of classification exist to divide patients into meaningful groups in order to better personalize their treatment regimens. Healthcare is evolving into more use of personalized treatments that can more effectively treat patients on an individual level, rather than by using more generalized treatments that may not prove effective in all patients. In addition, personalized treatment also aims to reduce adverse effects, while increasing effectiveness. Estrogen receptor (ER) status is one such method of grouping breast cancer patients into different treatment groups. Based on stage diagnosis and determination of receptor status, initial treatments such as surgery or radiotherapy may be used. Standard chemotherapy is another method, however, side effects may vary among patients and may be quite adverse. Other treatments include hormone or receptor blocking. This thesis has identified an alternatively spliced variant of classical ERα that resides in the plasma membrane of breast cancer cells and plays a major role in rapid signaling by estrogen. The overall aim of this thesis was to examine the role of the membrane receptor for 17β-estradiol (E2) in breast cancer that enhances breast tumor aggressiveness and to evaluate the mechanisms by which it functions. The general hypothesis was that nonclassical estrogen signaling through the proposed membrane-associated ER, ERα36, can promote breast tumor aggressiveness by enhancing cell survivability while altering expression of angiogenic and metastatic factors. This work examined the mechanisms of ERα36-dependent signaling in breast cancer cells, and the correlation of ERα36 to clinical outcome in human breast cancer tissue through histological evaluation. These data provide significant research as they provide a greater understanding of estrogen signaling in breast cancer through ERα36 and its role in tumorigenicity and metastasis. This study also proposes further clinical examination of ERα36, and suggests drug design to target ERα36 followed by preclinical studies to determine if drugs targeting ERα36 would benefit breast cancer patients by reducing tumorigenicity and increasing survival.
Advisors/Committee Members: Boyan, Barbara D. (advisor), Schwartz, Zvi (committee member), Shin, Chong (committee member), McCarty, Nael (committee member), Lobachev, Kirill S. (committee member).
Subjects/Keywords: Estrogen; Estrogen receptor-alpha 36; Cancer; Breast cancer; Plasma membrane; Tumor; Apoptosis; Angiogenesis; Metastasis
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APA (6th Edition):
Chaudhri, R. A. (2013). The role of estrogen receptor-Alpha 36 in the membrane effect of 17Beta-estra. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/52162
Chicago Manual of Style (16th Edition):
Chaudhri, Reyhaan Ali. “The role of estrogen receptor-Alpha 36 in the membrane effect of 17Beta-estra.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/52162.
MLA Handbook (7th Edition):
Chaudhri, Reyhaan Ali. “The role of estrogen receptor-Alpha 36 in the membrane effect of 17Beta-estra.” 2013. Web. 17 Apr 2021.
Vancouver:
Chaudhri RA. The role of estrogen receptor-Alpha 36 in the membrane effect of 17Beta-estra. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/52162.
Council of Science Editors:
Chaudhri RA. The role of estrogen receptor-Alpha 36 in the membrane effect of 17Beta-estra. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/52162
15.
Lee, Christopher S. D.
Directing the paracrine actions of adipose stem cells for cartilage regeneration.
Degree: PhD, Biomedical Engineering, 2012, Georgia Tech
URL: http://hdl.handle.net/1853/44713
► Current cartilage repair methods are ineffective in restoring the mechanical and biological functions of native hyaline cartilage. Therefore, using the paracrine actions of stem cell…
(more)
▼ Current cartilage repair methods are ineffective in restoring the mechanical and biological functions of native hyaline cartilage. Therefore, using the paracrine actions of stem cell therapies to stimulate endogenous cartilage regeneration has gained momentum. Adipose stem cells (ASCs) are an attractive option for this endeavor because of their accessibility, chondrogenic potential, and secretion of factors that promote connective tissue repair. In order to use the factors secreted by ASCs to stimulate cartilage regeneration, the signaling pathways that affect postnatal cartilage development and morphology need to be understood. Next, approaches need to be developed to tailor the secretory profile of ASCs to promote cartilage regeneration. Finally, delivery methods that localize ASCs within a defect site while facilitating paracrine factor secretion need to be optimized.
The overall objective of this thesis was to develop an ASC therapy that could be effectively delivered in cartilage defects and stimulate regeneration via its paracrine actions. The general hypothesis was that the secretory profile of ASCs can be tailored to enhance cartilage regeneration and be effectively delivered to regenerate cartilage in vivo. The overall approach used the growth plate as an initial model to study changes in postnatal cartilage morphology and the molecular mechanisms that regulate it, different media treatments and microencapsulation to tailor growth factor production, and alginate microbeads to deliver ASCs in vivo to repair cartilage focal defects.
Advisors/Committee Members: Boyan, Barbara D. (Committee Chair), Guldberg, Robert E. (Committee Member), Murphy, Mary (Committee Member), Sambanis, Anthanassios (Committee Member), Schwartz, Zvi (Committee Member).
Subjects/Keywords: Stem cells; Cartilage; Paracrine factors; Connective tissues; Connective tissues Growth; Chondrogenesis
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APA (6th Edition):
Lee, C. S. D. (2012). Directing the paracrine actions of adipose stem cells for cartilage regeneration. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/44713
Chicago Manual of Style (16th Edition):
Lee, Christopher S D. “Directing the paracrine actions of adipose stem cells for cartilage regeneration.” 2012. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/44713.
MLA Handbook (7th Edition):
Lee, Christopher S D. “Directing the paracrine actions of adipose stem cells for cartilage regeneration.” 2012. Web. 17 Apr 2021.
Vancouver:
Lee CSD. Directing the paracrine actions of adipose stem cells for cartilage regeneration. [Internet] [Doctoral dissertation]. Georgia Tech; 2012. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/44713.
Council of Science Editors:
Lee CSD. Directing the paracrine actions of adipose stem cells for cartilage regeneration. [Doctoral Dissertation]. Georgia Tech; 2012. Available from: http://hdl.handle.net/1853/44713
16.
Adams, Brandy Rogers.
Ceramic materials mimicking normal bone surface microstructure and chemistry modulate osteoblast response.
Degree: PhD, Biomedical Engineering (Joint GT/Emory Department), 2013, Georgia Tech
URL: http://hdl.handle.net/1853/50292
► Bone consists of collagen/hydroxyapatite (HA) composites in which poorly crystalline carbonated calcium phosphate is intercalated within the fibrillar structure. Normal bone mineral is a carbonated-apatite,…
(more)
▼ Bone consists of collagen/hydroxyapatite (HA) composites in which poorly crystalline carbonated calcium phosphate is intercalated within the fibrillar structure. Normal bone mineral is a carbonated-apatite, but there are limited data on the effect of mineral containing carbonate on cell response. Although the exact biological role of silicate in bone formation is unclear, silicate has been identified at trace levels in immature bone and is believed to play a metabolic role in new bone formation. To mimic the inorganic and organic composition of bone we have developed a variety of bone graft substitutes. In the present body of research, we characterized the surface composition of human cortical and trabecular bone. When then characterized the surface compositions of the following potential bone substitutes: carbonated hydroxyapatite (CO₃²-HA), silicated hydroxyapatite (Si-HA), and collagen sponges mineralized with calcium phosphate using the polymer-induced liquid-precursor (PILP) process. In the latter substitutes, the PILP process leads to type I collagen fibrils infiltrated with an amorphous mineral precursor upon which crystallization leads to intrafibrillar HA closely mimicking physiological bone mineral. We then determined the osteoblast-like cell response to each bone substitute to characterize the substrate’s effect on osteoblast differentiation. The observations collectively indicate that cells are sensitive to the formatting of the mineral phase of a bone substitute and that this format can be altered to modulate cell behavior.
Advisors/Committee Members: Boyan, Barbara B. (advisor), Schwartz, Zvi (committee member), Sandhage, Kenneth H. (committee member), Gower, Laurie (committee member), Babensee, Julia (committee member).
Subjects/Keywords: Osteoblast; Hydroxyapatite; Type I collagen; Bone; Biomedical materials; Ceramics in medicine; Bone regeneration; Bone substitutes
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APA ·
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APA (6th Edition):
Adams, B. R. (2013). Ceramic materials mimicking normal bone surface microstructure and chemistry modulate osteoblast response. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/50292
Chicago Manual of Style (16th Edition):
Adams, Brandy Rogers. “Ceramic materials mimicking normal bone surface microstructure and chemistry modulate osteoblast response.” 2013. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/50292.
MLA Handbook (7th Edition):
Adams, Brandy Rogers. “Ceramic materials mimicking normal bone surface microstructure and chemistry modulate osteoblast response.” 2013. Web. 17 Apr 2021.
Vancouver:
Adams BR. Ceramic materials mimicking normal bone surface microstructure and chemistry modulate osteoblast response. [Internet] [Doctoral dissertation]. Georgia Tech; 2013. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/50292.
Council of Science Editors:
Adams BR. Ceramic materials mimicking normal bone surface microstructure and chemistry modulate osteoblast response. [Doctoral Dissertation]. Georgia Tech; 2013. Available from: http://hdl.handle.net/1853/50292
Georgia Tech
17.
Fisher, Maya.
Bone marrow regeneration follwing tibial marrow ablation in rats is age dependent.
Degree: MS, Biology, 2008, Georgia Tech
URL: http://hdl.handle.net/1853/26526
► Objective: Injuries to the marrow cavity result in rapid bone formation followed by regeneration of the marrow. It is not known whether this process is…
(more)
▼ Objective: Injuries to the marrow cavity result in rapid bone formation followed by regeneration of the marrow. It is not known whether this process is affected by age, although the quality of marrow is markedly different in young and old animals. To test if marrow restoration differs with age, we used the rat tibial bone marrow ablation model, which has been used to examine calcification, osteointegration of metal implants, and remodeling of bone graft substitutes. Methods: Marrow was ablated in the left tibia of seven rats (rNu/rNu) per time point. At 0,7,14,21,28,35 and 42 days post-surgery, treated tibias and contralateral tibias were harvested and fixed in buffered formalin. Both tibias were scanned using microCT and trabecular and cortical BVF/TV calculated. Mid-sagittal sections of decalcified bones were stained with H&E and BVF/TV calculated. Results: MicroCT analysis of 1-month animals showed increased bone formation on day-7 and on day-21 the marrow was restored. Increased bone was seen in 3-month animals on day-7 and day-14, but it was significantly less than in 1-month rats. By day-21, trabecular bone was reduced by 50%. 10-month animals had less trabecular bone at day-7 and 14, but bone remained in the medullary canal through day-1. Histomorphometry indicated that bone formation peaked at day-7 in 1-month rats with remodeling underway by day-14. Bone formation in 3-month rats also peaked at day-7, but restoration occurred by day-21. However, in 10-month rats, peak bone occurred on day-14, with remodeling on day-28. Conclusions: Aged animals produced less primary bone than younger animals and remodeling was initiated later. Differences in micro-CT and histomorphometric analyses may reflect a reduction in calcification of the osteoid in the 10-month old animals. (Supported by Boston Scientific, Inc.)
Advisors/Committee Members: Boyan Barbara (Committee Chair), Guldberg Robert (Committee Member), Lovachev Kiril (Committee Member), Schwartz Zvi (Committee Member).
Subjects/Keywords: Ablation model; Trabecular bone; Bone marrow; Aging; Bone regeneration; Regeneration (Biology); Developmental biology
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APA (6th Edition):
Fisher, M. (2008). Bone marrow regeneration follwing tibial marrow ablation in rats is age dependent. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/26526
Chicago Manual of Style (16th Edition):
Fisher, Maya. “Bone marrow regeneration follwing tibial marrow ablation in rats is age dependent.” 2008. Masters Thesis, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/26526.
MLA Handbook (7th Edition):
Fisher, Maya. “Bone marrow regeneration follwing tibial marrow ablation in rats is age dependent.” 2008. Web. 17 Apr 2021.
Vancouver:
Fisher M. Bone marrow regeneration follwing tibial marrow ablation in rats is age dependent. [Internet] [Masters thesis]. Georgia Tech; 2008. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/26526.
Council of Science Editors:
Fisher M. Bone marrow regeneration follwing tibial marrow ablation in rats is age dependent. [Masters Thesis]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/26526
Georgia Tech
18.
Wong, Kevin L.
Caveolae and Caveolin-1 are important for Vitamin D signalling.
Degree: MS, Biomedical Engineering, 2010, Georgia Tech
URL: http://hdl.handle.net/1853/37086
► The most active form of Vitamin D, 1alpha,25(OH)2D3, modulates cells via receptor mediated mechanisms. While studies have elucidated the pathway via the classical nuclear Vitamin…
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▼ The most active form of Vitamin D, 1alpha,25(OH)2D3, modulates cells via receptor mediated mechanisms. While studies have elucidated the pathway via the classical nuclear Vitamin D Receptor (VDR), little is known about the membrane-associated Vitamin D Receptor (ERp60). Caveolae and its characteristic protein Caveolin-1 have been involved in many signaling pathways due to its specific structure and physical configuration. Other studies have shown that many components of the Vitamin D pathway have been found in caveolae. This study hypothesizes that caveolae and Caveolin-1 are important for the effects of 1,25 Vitamin D signaling via ERp60. Research up to date have shown that in rat and mouse growth zone chondrocytes, cells deprived of intact caveolae either through disruption through beta-Cyclodextrin or genetic knockout do not exhibit the characteristic responses to Vitamin D through ERp60 when compared to chondrocytes with functional caveolae. Studies using immunofluorescence co-localization and caveolae fractionation have shown that ERp60 is localized in the caveolae domains. Cellular fractionation was also performed to examine the localization of the ERp60 receptor in lipid rafts and caveolae. Histology and transmission electron microscopy were also used to examine the physiological importance of caveolae and Caveolin-1 in growth plate morphology and cellular characteristics.
Advisors/Committee Members: Boyan, Barbara (Committee Chair), Jo, Hanjoong (Committee Member), Rubin, Janet (Committee Member), Schwartz, Zvi (Committee Member).
Subjects/Keywords: Chondrocytes; Lipid raft; Cav-1 knockout mice; Matrix vesicles; Protein kinase C; Cartilage cells; Human physiology; Cholecalciferol; Vitamin D
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APA (6th Edition):
Wong, K. L. (2010). Caveolae and Caveolin-1 are important for Vitamin D signalling. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/37086
Chicago Manual of Style (16th Edition):
Wong, Kevin L. “Caveolae and Caveolin-1 are important for Vitamin D signalling.” 2010. Masters Thesis, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/37086.
MLA Handbook (7th Edition):
Wong, Kevin L. “Caveolae and Caveolin-1 are important for Vitamin D signalling.” 2010. Web. 17 Apr 2021.
Vancouver:
Wong KL. Caveolae and Caveolin-1 are important for Vitamin D signalling. [Internet] [Masters thesis]. Georgia Tech; 2010. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/37086.
Council of Science Editors:
Wong KL. Caveolae and Caveolin-1 are important for Vitamin D signalling. [Masters Thesis]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/37086
Georgia Tech
19.
Denison, Tracy Adam.
The effect of fluid shear stress on growth plate
chondrocytes.
Degree: PhD, Biomedical Engineering, 2009, Georgia Tech
URL: http://hdl.handle.net/1853/29603
► Cartilage tissue provides compressive resistance in diarthrodial joints, and has been shown to be regulated by mechanical signals, in particular with regard to production of…
(more)
▼ Cartilage tissue provides compressive resistance in diarthrodial joints, and has
been shown to be regulated by mechanical signals, in particular with regard to production
of extracellular matrix proteins. However, less is understood about how chondrocytes in
regions not solely purposed to provide compressive resistance may also be affected by
mechanical forces. The growth plate is a small layer of cartilage that functions to
facilitate longitudinal growth of the long bones from in utero through post-adolescent
development. The growth plate maintains distinct regions of chondrocytes at carefully
regulated stages of endochondral ossification that are in part characterized by their
morphology and differential responsiveness to vitamin D metabolites. Understanding if
mechanical cues could be harnessed to accelerate or delay the process of endochondral
ossification might be beneficial for optimizing tissue engineering of cartilage or
osteochondral interfaces. This study focused on three aims to provide a basis for future
work in this area: 1) Develop a cell line culture model useful for studying growth plate
chondrocytes, 2) Determine the response of primary growth plate chondrocytes and the
cell line model to fluid shear stress, and 3) determine if expression of integrin beta 1 is
important for the observed responses to shear stress. The findings of this study suggest
that inorganic phosphate can promote differentiation in coordination with the
24,25(OH)2D3 metabolite of vitamin D, and that fluid shear stress generally inhibits
differentiation and proliferation of growth plate chondrocytes in part through an integrin
beta 1 mediated pathway.
Advisors/Committee Members: Boyan, Barbara (Committee Chair), Schwartz, Zvi (Committee Co-Chair), Bonewald, Lynda (Committee Member), Jo, Hanjoong (Committee Member), Sambanis, Athanassios (Committee Member).
Subjects/Keywords: Cone-plate viscometer; Mechanotransduction; Orthopedic; Shear flow; Endochondral ossification; Cartilage cells; Chondrogenesis; Cartilage
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APA ·
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MLA ·
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Export
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Manager
APA (6th Edition):
Denison, T. A. (2009). The effect of fluid shear stress on growth plate
chondrocytes. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/29603
Chicago Manual of Style (16th Edition):
Denison, Tracy Adam. “The effect of fluid shear stress on growth plate
chondrocytes.” 2009. Doctoral Dissertation, Georgia Tech. Accessed April 17, 2021.
http://hdl.handle.net/1853/29603.
MLA Handbook (7th Edition):
Denison, Tracy Adam. “The effect of fluid shear stress on growth plate
chondrocytes.” 2009. Web. 17 Apr 2021.
Vancouver:
Denison TA. The effect of fluid shear stress on growth plate
chondrocytes. [Internet] [Doctoral dissertation]. Georgia Tech; 2009. [cited 2021 Apr 17].
Available from: http://hdl.handle.net/1853/29603.
Council of Science Editors:
Denison TA. The effect of fluid shear stress on growth plate
chondrocytes. [Doctoral Dissertation]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/29603
. 
Open Access Theses and Dissertations
