Metabolomic Profiles of Articular Cartilage Vary By Osteoarthritis Grade
Osteoarthritis (OA) is the most common chronic joint disease, characterized by the breakdown of the articular cartilage (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 metabolic differences in OA articular cartilage between grades III and IV in hopes of revealing potential drug targets. To accomplish this, AC from femoral heads were removed, homogenized, and metabolites were extracted for mass spectrometry analysis to generate metabolomic profiles of defined grades of OA. The results revealed that distinct metabolic phenotypes 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 associated with ascorbate metabolism, amino acid metabolism, fatty acid metabolism and vitamin metabolism (H, C, E, B5). These results suggest that radiography-confirmed grades III and IV OA are associated with distinct global metabolic phenotypes. The results of this study enhance our understanding of altered cartilage metabolism in OA which may lead to potential drug targets to slow, halt, or reverse cartilage damage in late stages of OA.