Energy crisis and cartilage collapse: metabolic reprogramming of chondrocytes in osteoarthritis

Osteoarthritis (OA), a degenerative joint disease imposing a significant global disease burden, exhibits pathological mechanisms far more complex than mere "cartilage wear". Previous research has long centered on mechanical wear of articular cartilage and inflammatory responses. However, recent studies reveal that metabolic reprogramming and energy metabolism disorders constitute core metabolic alterations in OA. This review centers on the link between the energy crisis in articular chondrocytes and cartilage collapse. It systematically examines evidence suggesting that impaired oxidative phosphorylation (OXPHOS), increased glycolysis, and altered metabolic substrates may contribute to OA pathogenesis by modifying the local microenvironment and epigenetic regulation, thereby promoting inflammation and extracellular matrix (ECM) degradation. Furthermore, this review synthesizes recent research to propose novel therapeutic hypotheses, suggesting that OA is a highly heterogeneous disease at the metabolic reprogramming level, and often initiated or exacerbated by pathological biomechanical loads. Future efforts should reclassify OA based on metabolic reprogramming to develop targeted therapies addressing distinct cellular metabolism pathways-such as glycolysis inhibitors, mitochondrial protectants, and glutaminase inhibitors.