Implications of obesity-mediated cellular dysfunction and adipocytokine signaling pathways in the pathogenesis of osteoarthritis

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, bone sclerosis, and chronic low-grade inflammation. Aging and injury play key roles in OA pathogenesis by triggering the release of proinflammatory factors from adipose tissue and other sources. Obesity and aging impair the function of endoplasmic reticulum (ER) chaperones, leading to ER stress, protein misfolding, and cellular apoptosis. Obesity also induces mitochondrial dysfunction in OA through oxidative stress and disrupts mitochondrial dynamics, exacerbating chondrocyte damage. These factors contribute to inflammation, matrix imbalance, and chondrocyte apoptosis. Adipocytes, the primary source of adipokines, release inflammatory mediators that affect joint cells. Several adipocytokines have a central role in the regulation of many aspects of inflammation. Adiponectin and leptin are the two most abundant adipocytokines that are strongly associated with OA progression. This literature review suggests that adipokines activate many signaling pathways to exert downstream effects and play significant roles in obesity-induced OA. Understanding this rapidly growing family of mainly adipocyte-derived mediators and obesity-mediated cellular dysfunction may be important in the development of new therapies for obesity-associated OA management. • Obesity is a major risk factor for osteoarthritis (OA). • Obesity can induce mitochondrial dysfunction and ER stress. • Mitochondrial dysfunction and ER stress are known to promote inflammation. • Adipocytes release adipokines and proinflammatory cytokines that are linked to OA. • Inhibitors of adipokine signaling pathways can improve patient outcomes in OA.