• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of TUScholarShareCommunitiesDateAuthorsTitlesSubjectsGenresThis CollectionDateAuthorsTitlesSubjectsGenres

    My Account

    LoginRegister

    Help

    AboutPeoplePoliciesHelp for DepositorsData DepositFAQs

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    INHIBITED MINERALIZATION IN OSTEOBLASTS CULTURED UNDER VARIED SIMULATED PARTIAL GRAVITY CONDITIONS AND THE USE OF PHYTONUTRIENTS FOR MITIGATING THE EFFECTS OF REDUCED GRAVITY

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    BraveboyWagner_temple_0225E_14 ...
    Size:
    4.113Mb
    Format:
    PDF
    Download
    Genre
    Thesis/Dissertation
    Date
    2022
    Author
    Braveboy-Wagner, Justin cc
    Advisor
    Lelkes, Peter I.
    Committee member
    Spence, Andrew J.
    Gerstenhaber, Jonathan Arye
    Marcinkiewicz, Cezary
    Lazarovici, Philip
    Department
    Bioengineering
    Subject
    Bioengineering
    Biomedical engineering
    Toxicology
    Cytoskeleton
    Mars
    Moon
    Osteoblast
    Polyphenol
    Simulated microgravity
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/7720
    
    Metadata
    Show full item record
    DOI
    http://dx.doi.org/10.34944/dspace/7692
    Abstract
    The multifaceted adverse effects of reduced gravity on the skeletal system pose a significant challenge to human spaceflight. There is an interest in investigating any hypothetical differences between partial gravity and microgravity, and in the unmet need to identify countermeasures to both. A hypothesis to be tested is that reduced gravity impairs a variety of osteogenic cell functions, such as proliferation and differentiation, and that these inhibitory effects can be mitigated by nutritional countermeasures or by interrupting signaling pathways that drive undesired osteogenic remodeling. Utilizing the Random Positioning Machine, it is possible to simulate a variety of reduced gravity levels relevant to future manned space missions: Mars, Moon, and Microgravity of the Low Earth Orbit (LEO) environment. In this study, the effects of altered gravity on the physiology and morphology of cultured osteoblasts were investigated, specifically on their proliferation, osteogenic differentiation, and matrix mineralization. In assessing the role of mechanotransduction in microgravity-induced cytoskeletal dysfunction, this thesis also explored whether selective inhibition of specific signaling steps within the Rho-ROCK pathway can be used to modulate the effects of microgravity on osteoblast differentiation and function. Finally, in developing new countermeasures, an investigation was made into the effectiveness of curcumin and carnosic acid, two nutritional antioxidants with pro-osteogenic properties, contrasted with the trace element zinc, as potential alimentary supplements that may mitigate or alleviate the deleterious effects of microgravity. Results showed that short-term (6 days) culture yielded a dose-dependent reduction in proliferation and the enzymatic activity of alkaline phosphatase (ALP), while long-term studies (21 days) showed a distinct dose-dependent inhibition of mineralization. By contrast, expression levels of key osteogenic genes (Alkaline phosphatase, Runt-related Transcription Factor 2, Sparc/osteonectin) exhibited a threshold behavior: gene expression was significantly inhibited when the cells were exposed to Mars-simulating partial gravity, and this was not reduced further when the cells were cultured under simulated Moon or microgravity conditions. My data suggests that impairment of cell function with decreasing simulated gravity levels is graded and that the threshold profile observed for reduced gene expression is distinct from the dose dependence observed for cell proliferation, ALP activity, and mineral deposition. My studies into the gravity-induced re-organization of the cytoskeleton indicate that selective interruption of the Rho-ROCK pathway at ROCK can prevent morphological changes that result in impaired differentiation and mineralization. Further, I found that nutraceuticals partially reversed the inhibitory effects of SMG on ALP activity and promoted osteoblast proliferation and differentiation in the absence of traditional osteogenic media. I further observed a synergistic effect of the intermix of the phytonutrients on ALP activity. Intermixes of phytonutrients may serve as convenient and effective nutritional countermeasures against bone loss in space.
    ADA compliance
    For Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2022)  DuraSpace
    Temple University Libraries | 1900 N. 13th Street | Philadelphia, PA 19122
    (215) 204-8212 | scholarshare@temple.edu
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.