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dc.contributor.advisorMary L. Bouxsein and Paola Divieti Pajevic.en_US
dc.contributor.authorSpatz, Jordan Matthewen_US
dc.contributor.otherHarvard--MIT Program in Health Sciences and Technology.en_US
dc.date.accessioned2016-02-29T15:01:09Z
dc.date.available2016-02-29T15:01:09Z
dc.date.copyright2015en_US
dc.date.issued2015en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/101338
dc.descriptionThesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2015.en_US
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractA human mission to Mars will be physically demanding and presents a variety of medical risks to crew members. It has been recognized for over a century that loading is fundamental for bone health, and that reduced loading, as in prolonged bed rest or space flight, leads to bone loss. Osteocytes, the most abundant bone cell type, are thought to be key mechanical sensors in bone, yet the molecular mechanism of this action remains poorly understood. Improved understanding of how osteocytes regulate skeletal responses to mechanical loading and unloading could have significant implications for treatment of bone disorders related to disuse or immobilization. Thus, we conducted in vitro and in vivo studies on osteocytes exposed to unloading to investigate their role in disuse and microgravity-induced bone loss. Specifically, we generated and characterized a novel osteocytic cell line that recapitulates the response to hormonal and mechanical stimuli of osteocytes in vivo. This novel cell line provided the first evidence of a cell-autonomous increase in sclerostin, a potent inhibitor of Wntsignaling, following exposure to simulated microgravity. These cells were also used for a spaceflight mission after demonstrating their ability to maintain an osteocytic phenotype when cultured in a fully automated flight-certified system. Finally, we utilized murine models of unloading to show that pharmacologic inhibition of sclerostin induces bone formation and prevents disuse-induced bone loss.en_US
dc.description.statementofresponsibilityby Jordan Matthew Spatz.en_US
dc.format.extent155 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectHarvard--MIT Program in Health Sciences and Technology.en_US
dc.titleThe role of osteocytes in disuse and microgravity-induces bone lossen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentHarvard--MIT Program in Health Sciences and Technology.en_US
dc.identifier.oclc938897490en_US


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