Enhancing Oxidative Phosphorylation Through Inhibition Of Pdk2 Alleviates Cartilage Degradation In A Surgical Model Of Osteoarthritis

Purpose: Although chondrocytes rely primarily on glycolysis to meet their cellular energy needs, they have the metabolic flexibility to shift toward oxidative phosphorylation (OxPhos) in the early stage of osteoarthritis (OA). As the disease progresses, however, this metabolic adaptation of OA cartilage reaches its limit and eventually fails, resulting in mitochondrial dysfunction and oxidative stress which are hallmarks of OA. The objective of this study was to determine whether the modulation of OxPhos through pyruvate dehydrogenase kinase (PDK)-2 affects metabolic flexibility of chondrocytes, and cartilage degeneration in surgical model of OA.