most studies though point to the latter (61),as leptin was shown to activate nitric oxide synthase and activation of MMPs all of which exert detrimental effect on articular cartilage (56,62-64).another interesting aspect of leptin in OA was investigated in advanced and minimally affected osteoarthritic cartilage where leptin and leptin’s receptor (Ob-Rb) expression levels were significantly elevated in advanced OA cartilage compared to minimally affected cartilage (59).