Dysregulation of the glycolysis-mitochondrial metabolism axis in osteoarthritis: mechanisms and therapeutic implications.

Osteoarthritis (OA) is a chronic degenerative joint disease affecting more than 595 million people worldwide. Progressive cartilage degeneration is closely linked to metabolic reprogramming in chondrocytes. Unlike other joint-resident cells, chondrocytes rely on a distinctive, largely glycolysis-dependent mode of glucose utilisation that must be tightly regulated to maintain cellular homeostasis. Glucose metabolism spans cytosolic glycolysis and mitochondrial oxidative phosphorylation, and growing research has clarified how each contributes to the pathophysiology of OA. Building on these advances, we synthesise current mechanistic evidence to conceptualise chondrocyte glucose metabolism as an integrated continuum, proposing the glycolysis-mitochondrial metabolism-OA axis as a unifying framework. We outline how axis disruption provides a coherent lens for understanding metabolic dysfunction in OA, and we highlight mechanistic insights with translational potential, including candidate targets that may support future diagnosis and therapy. Together, this literature review aims to sharpen the conceptual link between metabolic homeostasis and cartilage integrity, and to guide the development of mechanism-informed strategies for degenerative joint disease. The translational potential of this article: This literature review outlines the mechanistic framework of a glycolysis-mitochondrial metabolism-OA axis and highlights actionable biomarkers and integrated therapeutic strategies that may guide the development of dual-target interventions for precision OA treatment.