Targeting parkin-regulated metabolomic change in cartilage in the treatment of osteoarthritis II

Articular cartilage degeneration, which may lead to osteoarthritis (OA), is a normal component of the aging process, but its underlying mechanism remains unknown. We found that chondrocytes exhibited an energy metabolism shift from glycolysis to oxidative phosphorylation (OXPHOS) during aging. Reprogrammed cartilage metabolism by parkin ablation decreased OXPHOS and increased glycolysis, with ameliorated aging-related OA. Metabolomics analysis indicated that lauroyl-L-carnitine (LLC) was decreased in aged cartilage, but increased in parkin-deficient cartilage. In vitro, LLC improved the cartilage matrix synthesis of OA chondrocytes. In vivo, intraarticular injection of LLC in mice with anterior cruciate ligament transaction (ACLT) ameliorated OA. These results suggest that metabolic changes are regulated by parkin-impaired cartilage during aging, and targeting the metabolomic changes by supplementation with LLC is a promising treatment strategy for ameliorating OA. To investigate the expression change regulated by parkin in articular cartilage