Inflammatory mechanisms underlying metabolic syndrome-associated and potential treatments.

Objectives: Osteoarthritis (OA), a debilitating disease, has been recognized as a heterogenous disease, with metabolic syndrome-associated osteoarthritis (MetS-OA) emerging as a significant area of interest. Currently, the understanding of MOA remains limited, with a prevailing consensus attributing its etiology to the core components of metabolic syndrome: obesity, hyperglycemia, dyslipidemia, and hypertension. The aim of this review is to summarize the current understanding of the complex relationship between metabolic syndrome and OA from the perspectives of epidemiology and molecular biology, and to explore potential targeting strategies for metabolic syndrome in MetS-OA management. Methods: This narrative review evaluated literature (2010-2024) from PubMed, examining clinical and mechanistic evidence linking metabolic syndrome to OA, including therapeutic studies targeting MetS-OA. Results: Metabolic syndrome aggravate the cartilage injury in MetS-OA through metabolic biomarkers (adipokines, advanced glycation end-products and oxidized LDL), metabolic responses (oxidative stress, insulin resistance and ischemic hypoxic injuries), and abnormally activated cells (adipocytes and macrophages). It ultimately lead to the aggravation of synovitis in MetS-OA through inflammatory mediators. Conclusions: The exploration of the relationship between metabolic syndrome and OA could benefit the development of targeting strategies for MetS-OA, including currently FDA-approved drugs for the treatment of metabolic syndrome and potential drugs targeting metabolic factors, which might provide a novel avenue for the future management of MetS-OA.