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dc.contributor.authorParker, Emily
dc.date.accessioned2022-06-22T19:11:39Z
dc.date.available2022-06-22T19:11:39Z
dc.date.issued2022-07-13
dc.identifier.urihttp://hdl.handle.net/10675.2/624295
dc.description.abstractLoss of skeletal muscle is associated with an increased risk of falls, fractures, and mortality. Muscle atrophy can occur in settings such as prolonged bed rest, spinal cord injury, aging and spaceflight, and is often accompanied by bone loss; however, the cellular and molecular mechanisms underlying muscle and bone atrophy remain poorly understood. Fibro-adipogenic progenitor cells (FAPs) play a significant role in maintaining skeletal muscle mass through their complex secretome, but their role in disuse atrophy has not been explored. This study tests the hypothesis that muscle disuse alters the FAP secretome, contributing to muscle atrophy and bone loss. Results show that FAPs isolated from immobilized muscle have increased expression of IL-1β and Cdkn2a (p16INK4A), factors that can induce muscle cell atrophy and senescence, respectively. On the other hand, IL-1β depletion in IL-1β deficient knockout mice attenuates muscle atrophy with immobilization. Moreover, mice lacking IL-1β do not lose bone strength with immobilization and do not increase bone resorption. Hindlimb immobilization was also found to significantly alter the microRNA cargo of FAP-derived extracellular vesicles (EVs), but changes in these miRNAs were not observed in EVs from IL-1β deficient mice. Overall, our data suggest that FAP-derived IL-1β plays an important role in the muscle atrophy and bone loss that occur with disuse, and thus may represent a potential therapeutic target for improving muscle and bone function in settings of unloading.
dc.publisherAugusta University
dc.subjectCellular biology
dc.subjectfibro-adipogenic progenitors, IL-1β, immobilization, muscle atrophy, SASP
dc.titleTHE ROLE OF FIBRO-ADIPOGENIC PROGENITOR CELLS (FAPS) IN MUSCLE DISUSE ATROPHY
dc.typedissertationen_US
dc.contributor.departmentBiomedical Sciences
dc.language.rfc3066en
dc.date.updated2022-06-22T19:11:40Z
dc.description.advisorHamrick, Mark
dc.description.committeeIsales, Carlos
dc.description.committeeFulzele, Sadanand
dc.description.committeeMcGee-Lawrence, Meghan
dc.description.committeeTang, Yao-Liang
dc.description.committeeLiu, Yutao
dc.description.degreePh.D.
dc.description.embargo06/22/2023


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