An update on the association between metabolic syndrome and osteoarthritis and on the potential role of leptin in osteoarthritis.

Metabolic syndrome (MetS) has been associated with osteoarthritis (OA). Leptin, which is one of the markers of MetS, has been associated with OA pathophysiology. This study aimed to provide an update on the association between MetS and OA and on the potential role of leptin in OA. In this review, we summarized the current knowledge of the association between MetS and OA and updated the evidence on the potential role of leptin in OA. Clinical studies have investigated the epidemiologic association between MetS or its components and OA. Results suggested strong epidemiologic associations between MetS and OA, especially in the Asian population. Animal studies also indicated that metabolic dysregulation may lead to OA pathogenesis. The systemic role of MetS in OA pathophysiology is associated with obesity-related inflammation, the beneficial role of n-3 polyunsaturated fatty acids and deleterious role of cholesterol, physical inactivity, hypertension-induced subchondral ischemia, dyslipidemia-induced ectopic lipid deposition in chondrocytes, hyperglycemia-induced local effects of oxidative stress and advanced glycation end-products, low-grade systemic inflammation, and obesity-related adipokines by inducing the expression of proinflammtory factors. Leptin levels in serum/plasma and synovial fluid were associated with joint pain, radiographic progression, bone formation biomarkers, cartilage volume, knee OA incidence, and total joint arthroplasty in OA patients. Elevated leptin expression and increased effect of leptin on infrapatellar fat pad, synovium, articular cartilage, and bone were also involved in the pathogenesis of OA. Current knowledge indicates a convincing epidemiologic association between MetS and OA, especially in the Asian population. Animal studies have also shown that metabolic dysregulation may lead to OA pathogenesis. Accumulating evidence suggests that leptin may play a potential role in OA pathogenesis. Therefore, leptin and its receptor may be an emerging target for intervention in metabolic-associated OA.