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

steoarthritis (OA) is a frequent comor- bidity in obese patients, which signifi- cantly impacts their quality of life and represents a common cause of disability. The pathogen- esis 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 obesi- 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 proin- flammatory cytokines, the degeneration of articular car- tilage in OA is highly dependent on inflammatory path- ways. Understanding the pathophysiology of OA allows for the inclusion of new therapeutic targets. Neverthe- less, more research is needed to properly comprehend the pathophysiology of OA and to implement new strate- gies accordingly. This review aims to analyze the mo- lecular mechanisms associated with mechanical over- load and their participation in the origin of OA; likewise, other mechanisms associated with obesity will also be reviewed.