1-Determine the effects of microgravity and partial microgravity on bone loss and long-term recovery using rat suspension models. Our working hypothesis is that microgravity (0 g) and partial microgravity (1/3 g and 1/6 g) will alter bone remodeling leading to a long-term bone loss. Micro Computed Tomography (MicroCT) and histomorphometric analysis of bone formation and resorption will be conducted to determine microstructural changes. Mechanical testing will be used to assess structural integrity. The genomic effects of microgravity will be evaluated using RNAseq to identify differentially expressed signaling pathways. Longitudinal analysis of serum levels of bone markers will be conducted using ELISA analysis.
2-Assess the efficacy of periodic hypergravity during simulated microgravity and partial microgravity as countermeasures to mitigate microgravity-induced short term and long term effects on bone integrity. Our working hypothesis is that hypergravity will provide essential mechanical stimulation to restore microgravity and partial microgravity-induced impairment of bone remodeling. The efficacy of periodic hypergravity will be determined using bone microstructural analyses (Micro CT, bone formation, and resorption histomorphometry), mechanical analysis (three-point testing), genomic (RNA seq), and serum biomarker analysis (ELISA).
Significance and Outcomes: Bone remodeling is a complex process that is tightly regulated by osteoblast-osteoclast coupling and communication. Microgravity impairs this process by increasing osteoclast associated resorption and decreasing osteoblastic bone formation. In order to continue to expand our crewed spaceflight program, it is essential to determine the effects of microgravity on bone remodeling and develop targeted countermeasures to sustain bone health in microgravity and partial microgravity.
This experiment is currently in progress. Results will be available at the conclusion of the study.
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