Pathogenesis of knee osteoarthritis in obese patients: mechanical overload and molecular mechanisms

Osteoarthritis (OA) is a frequent comorbidity in obese patients, which significantly impacts their quality of life and represents a common cause of disability. The pathogenesis of OA is often related to overuse and mechanical overload, which are markedly present in obese patients. However, this approximation oversimplifies the complex metabolic and inflammatory pathways connecting obesity and OA. Indeed, other frequent obesity comorbidities like diabetes, hypertension, and metabolic syndrome are closely related to OA. Moreover, low-grade chronic inflammation, an obesity hallmark, is associated with articular cartilage damage through several pathways. Furthermore, mechanical overload is a mechanism that depends on several molecular pathways. From the role of mechanosensitive receptors to the induction of proinflammatory cytokines, the degeneration of articular cartilage in OA is highly dependent on inflammatory pathways. Understanding the pathophysiology of OA allows for the inclusion of new therapeutic targets. Nevertheless, more research is needed to properly comprehend the pathophysiology of OA and to implement new strategies accordingly. This review aims to analyze the molecular mechanisms associated with mechanical overload and their participation in the origin of OA; likewise, other mechanisms associated with obesity will also be reviewed.