Time Course of Metabolic Shifts in Cartilage Explants Exposed to Short-Term Simulated Microgravity

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Authors
Houske, Eden
Chapman, Marrin
Bourekis, Kiki
Advisor
Hahn, Alyssa
Editor
Date of Issue
2023-04-28
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Title
Time Course of Metabolic Shifts in Cartilage Explants Exposed to Short-Term Simulated Microgravity
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Presentation
Description
Abstract
Evidence suggests that abnormal mechanical loading leads to an imbalance in chondrocyte metabolism that results in cartilage degeneration – a hallmark of osteoarthritis (OA). Microgravity exposure in space reduces mechanical loads, potentially leading to increased catabolic activity of chondrocytes and the development of OA. This study aimed to assess how chondrocyte metabolism is altered in response to simulated microgravity (SM) exposure to gain insight into the mechanisms responsible for cartilage degeneration in reduced-loading environments. Healthy post-mortem human cartilage explants were exposed to SM for 1 or 4 days using a Rotating Wall Vessel (RWV) bioreactor with the remaining control explants exposed to normal gravitational forces. A subset of the control and SM explants were analyzed for cell viability by staining and measuring relative fluorescence units. Metabolites were extracted from explants and surrounding media and data were generated by liquid chromatography-mass spectrometry. Pathways upregulated in response to SM include pyrimidine, amino acid, and sugar metabolism which may be suggestive of extracellular matrix remodeling. Changes in metabolites secreted from explants into the surrounding media mapped to lysine and vitamin E metabolism. These have been previously detected in human synovial fluid from osteoarthritic donors, suggesting that even short-term SM exposure may induce metabolic shifts similar to that of early OA. Notably, this is the first study to map global metabolic changes in cartilage in response to short-term SM exposure to gain insight into the risk of developing OA post-spaceflight.
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Semester
Spring
Department
Biology