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You searched for +publisher:"Penn State University" +contributor:("Henry Joseph Donahue, Dissertation Advisor/Co-Advisor"). Showing records 1 – 3 of 3 total matches.

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Penn State University

1. Govey, Peter Michael. Multiscale Anabolic Bone Responses to Fluid Flow and Post-irradiation Loading.

Degree: 2015, Penn State University

The long-term goal of this work is to reduce the burden of skeletal fractures by learning how to appropriate and guide the body’s inherent capacity for adaptive bone formation. This tissue-level adaptation to mechanical load is the end product of bone cells responding to physical phenomena in their microscopic niche. Our objective was to elucidate if, and how, the initial stimulation of cells might ultimately bring about bone adaptation to strengthen bones at risk for fracture, specifically those damaged by radiation therapy. Our study followed that sequence: we first examined the response of osteocytic cells—those thought to orchestrate the adaptive response—to in vitro fluid flow simulating the physical stimulation present at the microscopic scale upon loading. We identified novel cell signaling using high-throughput analyses of the whole gene transcriptome and proteome, enriched by network mapping and functional association databases. These results implicated inflammatory cellular recruitment, most notably via up-regulation of stem cell homing chemokines Cxcl1 and Cxcl2. Therefore, we examined recruitment of cells to loaded bones as we progressed to the whole tissue scale of adaptation. First, in mice in vivo, we determined compression loading was best suited for examining both trabecular and cortical tibia bone adaptation since cantilever loading brought about trabecular bone loss. Importantly, compression loading attenuated bone loss, and even added additional new bone in mice modeling our at-risk population of irradiated bone marrow transplant recipients. Hence, we propose that cancer and transplant patients subject to similar therapies may also retain robust physiological capacity for load-induced bone adaptation to alleviate fracture risk. To unify these cell- and tissue-scale observations, we examined recruitment of transplanted donor cells. We found no up-regulation of donor cell proportions in marrow of loaded bones, but a non-significant trend toward increased donor cell presence in loaded bone itself. In sum, these findings lead us to propose that when irradiated bones are loaded, fluid flowed osteocytes signal for recruitment of marrow- or vasculature-derived osteoprogenitors, thereby increasing adaptive bone formation and fracture resistance. Advisors/Committee Members: Henry Joseph Donahue, Dissertation Advisor/Co-Advisor, Justin Lee Brown, Committee Member, Gregory Stephen Lewis, Committee Member, Christopher Niyibizi, Committee Member, Christopher Alan Siedlecki, Committee Member.

Subjects/Keywords: bone; mechanical loading; fluid flow; bone adaptation; radiation; irradiation; stem cell; mechanotransduction; bone marrow

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Govey, P. M. (2015). Multiscale Anabolic Bone Responses to Fluid Flow and Post-irradiation Loading. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/25657

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):

Govey, Peter Michael. “Multiscale Anabolic Bone Responses to Fluid Flow and Post-irradiation Loading.” 2015. Thesis, Penn State University. Accessed March 03, 2021. https://submit-etda.libraries.psu.edu/catalog/25657.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Govey, Peter Michael. “Multiscale Anabolic Bone Responses to Fluid Flow and Post-irradiation Loading.” 2015. Web. 03 Mar 2021.

Vancouver:

Govey PM. Multiscale Anabolic Bone Responses to Fluid Flow and Post-irradiation Loading. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Mar 03]. Available from: https://submit-etda.libraries.psu.edu/catalog/25657.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Govey PM. Multiscale Anabolic Bone Responses to Fluid Flow and Post-irradiation Loading. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/25657

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

2. Lloyd, Shane. The Role of Connexin43 Gap Junction Protein in the Musculoskeletal Changes Induced by Mechanical Unloading.

Degree: 2013, Penn State University

Connexin43 (Cx43) is the predominant gap junction protein in bone. In the present study we examined the role of Cx43 in the skeletal response to mechanical unloading (i.e., lack of weight bearing). Mechanical unloading induces significant bone loss and muscle atrophy. A better understanding of the mechanisms underlying these deleterious effects is required in order to identify novel targets for therapeutic countermeasures. First, we collected tissue from mice following 0, 7, 14, and 21 days of hindlimb suspension (HLS) or normal loading. We found that muscle atrophy (due to decreased protein synthesis and increased protein degradation) precedes bone loss during mechanical unloading. Reduced mechanical force due to muscle atrophy may compound bone loss associated with a lack of weight bearing. Furthermore, age-related trabecular bone loss in mice, similar to that which occurs in mature astronauts, is superimposed on unloading. Preservation of muscle mass, cortical bone structure, and overall bone strength with age in normally loaded control mice suggests that muscle has a greater effect on cortical versus trabecular bone. Next, we sought to determine the role of Cx43 in unloading-induced bone loss by subjecting mice with a bone-specific deletion of Cx43 (cKO) to HLS. Following three weeks of HLS, wild-type (WT) mice experienced substantial bone loss; however, these deleterious effects were attenuated in cKO mice. Unloading also suppressed bone formation in WT mice, while there was no change from baseline for cKO-Suspended. mRNA levels of the gene encoding sclerostin, an osteocyte-derived inhibitor of bone formation, were greater in WT-Suspended, whereas cKO-Suspended was unchanged. The proportion of sclerostin-positive osteocytes was significantly lower in cKO-Control versus WT-Control, a difference accounted for by the presence of numerous empty lacunae and apoptotic osteocytes. There was no change in trabecular osteocyte viability. Osteoclast indices were lower in Suspended cKO versus WT-Suspended. Osteocyte apoptosis induced by Cx43 deficiency appears to preserve bone structure by preventing both suppression of bone formation and increased bone resorption during mechanical unloading. Attenuated trabecular bone loss, despite an apparent lack of affect on osteocyte viability in this compartment, suggests that an additional mechanism, independent of osteocyte apoptosis, may also be important. Advisors/Committee Members: Henry Joseph Donahue, Dissertation Advisor/Co-Advisor, Henry Joseph Donahue, Committee Chair/Co-Chair, Charles H Lang, Committee Member, Neil Sharkey, Committee Member, James Robert Connor, Committee Member, Alicia Ellen Bateman, Special Member.

Subjects/Keywords: connexin43; unloading; bone loss; sclerostin; osteocyte; apoptosis; RANKL; muscle; spaceflight; atrophy; osteopenia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Lloyd, S. (2013). The Role of Connexin43 Gap Junction Protein in the Musculoskeletal Changes Induced by Mechanical Unloading. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/18342

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):

Lloyd, Shane. “The Role of Connexin43 Gap Junction Protein in the Musculoskeletal Changes Induced by Mechanical Unloading.” 2013. Thesis, Penn State University. Accessed March 03, 2021. https://submit-etda.libraries.psu.edu/catalog/18342.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Lloyd, Shane. “The Role of Connexin43 Gap Junction Protein in the Musculoskeletal Changes Induced by Mechanical Unloading.” 2013. Web. 03 Mar 2021.

Vancouver:

Lloyd S. The Role of Connexin43 Gap Junction Protein in the Musculoskeletal Changes Induced by Mechanical Unloading. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 03]. Available from: https://submit-etda.libraries.psu.edu/catalog/18342.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lloyd S. The Role of Connexin43 Gap Junction Protein in the Musculoskeletal Changes Induced by Mechanical Unloading. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/18342

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Penn State University

3. Chin-quee, Karis P. Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look .

Degree: 2013, Penn State University

ABSTRACT Successful metastasis requires some degree of hospitality from the host organ that is metastasized. In recent years, evidence has been mounting that the primary tumor contributes to adapting this remote organ to increase this hospitality. Interestingly, many in vitro experiments have shown that conditioned media from cancer cells produce physical changes which theoretically could facilitate invasion. These include perturbations in extracellular matrix and of cell to cell adhesions. The conditioned media in these in vitro experiments could be interpreted to be a proxy for either paracrine or endocrine effects, however, when these observations are coupled with evidence from in vivo experiments, it seems possible that primary tumors have remote effects on un-metastasized organs that can elicit changes in them which are pro-metastatic. We have performed a series of experiments designed to characterize and describe changes in osteoblasts (hFOB) which occur as a result of exposure to conditioned medium from breast cancer cells (MDA-MET). Functional experiments aimed at investigating whether these changes are pro-metastatic were included as a means of this characterization. Thus cell to cell adhesions, as well as the ability of the osteoblastic environment to attract MDA-MET cells were both assessed. Further, we investigated mechanistically the bases behind the observations from the functional experiments. Methods Confluent hFOB cells were treated with conditioned media from either MDA-MET, MDA-MB-231 HTERT-HME1 or hFOB cells 24 hrs. This treatment conditioned medium was removed, the cells washed and serum-free medium added to the hFOB cells. hFOB-conditioned medium was collected after 18hrs. This medium was then used in in vitro migration assays measuring number of MDA-MET migratory cells by labeling the cells with DNA-binding dye Cyquant; in establishing presence of collagen by western blot; in collagenase assays and in a cytokine array where antibodies to 74 cytokines were embedded on a membrane. The presence of Type 1 collagen receptors was shown by immunocytochemistry. The data were analyzed using one way ANOVA and the Student’s T test. Results We found that conditioned medium from hFOB cells that had been treated with MDA-MET-conditioned medium attracted more MDA-MET cells than hFOB cells pre-exposed to its own medium only. We hypothesized that Type 1 collagen fragments of specific length were the chemoattractants responsible for our observed effect. This was evidenced by an increase in collagenase in the conditioned medium of hFOB cells which had been exposed to MDA-MET-conditioned medium. The definitiveness of this evidence was aided by the inherent fidelity of the collagenase enzymes and its Type 1 collagen substrate and the distinctiveness of the product of this enzyme substrate interaction. We also showed that bacterial collagenase, which creates short collagen fragments of non-specific length removed the ability of hFOB -conditioned medium to attract MDA-MET cells. In addition, we showed that at… Advisors/Committee Members: Henry Joseph Donahue, Dissertation Advisor/Co-Advisor, Henry Joseph Donahue, Committee Chair/Co-Chair, Andrea Manni, Committee Member, Andrea Marie Mastro, Committee Member, David Feith, Committee Member, Lisa M Shantz, Committee Member, Ralph Lauren Keil, Committee Member.

Subjects/Keywords: breast cancer metastasis; pre-metastatic niche; bone; collagen fragments; collagenase

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Chin-quee, K. P. (2013). Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17496

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):

Chin-quee, Karis P. “Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look .” 2013. Thesis, Penn State University. Accessed March 03, 2021. https://submit-etda.libraries.psu.edu/catalog/17496.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Chin-quee, Karis P. “Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look .” 2013. Web. 03 Mar 2021.

Vancouver:

Chin-quee KP. Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look . [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 03]. Available from: https://submit-etda.libraries.psu.edu/catalog/17496.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chin-quee KP. Breast cancer cell secretions promote a pre-metastatic niche in bone; an in vitro look . [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/17496

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.