Time Course of Metabolic Shifts in Cartilage Explants Exposed to Short-Term Simulated Microgravity
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Authors
Houske, Eden
Date of Issue
2023
Type
Thesis
Language
en_US
Subject Keywords
Other Titles
Abstract
Abnormal mechanical joint loading leads to an imbalance in chondrocyte metabolism that results in cartilage degeneration – a hallmark of osteoarthritis (OA). Microgravity exposure in space significantly reduces mechanical loads applied to the joints, leading to increased catabolic activity of chondrocytes and thus increasing the risk of OA. This study assesses 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 one or four days using a Rotating Wall Vessel (RWV) bioreactor and compared with the 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. Metabolites were extracted from explants and surrounding media, and data were generated by liquid chromatography-mass spectrometry. Pathways upregulated in response to SM include the metabolism of pyrimidine, amino acids, and sugars, 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 pathway changes 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 study is the first 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.