Why NASA should care about osteoarthritis: Metabolomic Analyses to Provide Insight into the Risk of Joint Unloading in Microgravity Environments

Abstract

A recurring issue NASA faces is the health of their space crews’ before, during, and after space missions due to microgravity. A lack of joint loading is known to reduce articular cartilage (AC) thickness and increase the risk of osteoarthritis (OA). OA is the most common chronic joint disease, characterized by the breakdown of the AC. However, there are currently no therapeutic drug targets to slow the progression of disease because disease pathogenesis is largely unknown. Thus, the goals of this study were to (1) spatially map metabolism across regions of OA cartilage and (2) identify any differences in OA articular cartilage grades III vs. IV in hopes of revealing potential drug targets. To accomplish this, AC from femoral heads were removed, homogenized, and metabolites were extracted to generate metabolomic profiles of defined grades of OA. We found that distinct metabolic phenotypes do exist between articular cartilage from grades III and IV OA hip joints, but not across different regions of the diseased joint. The pathways that contributed the most to these differences between grades were vitamin metabolism (C, E, B5), amino acid metabolism, and fatty acid oxidation. These results suggest that radiography-confirmed grades of OA are associated with distinct global metabolic phenotypes in AC, revealing distinct potential drug targets in each grade of OA. The results of this study enhance our understanding of OA pathogenesis and revealed potential drug targets for the treatment of OA.