Characterization of Metabolomic Profiles of Encapsulated Chondrocytes Exposed to Short-Term Simulated Microgravity: A Pilot Study
Date of Issue2022
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TitleCharacterization of Metabolomic Profiles of Encapsulated Chondrocytes Exposed to Short-Term Simulated Microgravity: A Pilot Study
AbstractMechanical loading of cartilage stimulates chondrocyte metabolism to maintain cartilage integrity. Shifts from physiological loading conditions, such as overloading or reduced loading, can lead to an imbalance in chondrocyte metabolism, leading to early osteoarthritis (OA). This is of particular concern in space, where reduced mechanical forces during prolonged microgravity exposure (10-6 G) could lead to OA and compromise flight crew mobility, resulting in incomplete mission duties. Thus, the goal of this pilot study was to expand our understanding of the risk of developing OA post spaceflight through a deeper understanding of chondrocyte mechanotransduction. To do this, we encapsulated human chondrocytes in an agarose gel of similar stiffness to the pericellular matrix to better stimulate the cartilage microenvironment and exposed these encapsulated chondrocyte constructs to simulated microgravity (SM) using a rotating wall vessel (RWV) bioreactor. We analyzed the response to SM using global metabolomic profiling to gain an untargeted and unbiased view of metabolic shifts. These results suggest that short-term (<4 days) exposure to microgravity does not induce large-scale shifts in chondrocyte metabolism. However, the metabolic shifts that occurred in response to microgravity exposure were consistent with early OA metabolomic profiles in human synovial fluid which could suggest that even short-term exposure to microgravity may lead to the development of OA. This work enhances our ability to study chondrocyte mechanotransduction in SM in vitro by encapsulating chondrocytes in a three-dimensional agarose construct of relevant physiological stiffness that better stimulates the cartilage microenvironment.
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