186 TOLL-LIKE RECEPTORS ACTIVATE THE ESE-1 PROMOTER IN CHONDROCYTES BY A MECHANISM PARTIALLY DEPENDENT UPON NF-κB

Abstract

ing insulin sensitivity. Recently, adiponectin has also been found to regulate immune responses and inflammation. Adiponectin is found in OA joints but its role in the pathogenesis of OA and in cartilage metabolism is not clear. In the present study, we investigated the relation of circulating adiponectin and biomarkers of cartilage degradation (COMP and MMP-3) in patients with OA, and the effects of adiponectin on human OA cartilage. Methods: Blood samples were collected from 38 male OA patients (BMI 29.5±0.8 kg/m2) undergoing knee replacement surgery because of severe OA, and adiponectin, COMP and MMP-3 concentrations were measured by immunoassay. Cartilage samples collected from OA patients under total knee arthroplasty were placed in tissue culture and exposed to adiponectin. Results: Plasma adiponectin (2.5±0.2 μg/ml) correlated positively with serum COMP (r=0.55, p=0.001) and plasma MMP-3 (r=0.34, p=0.046). In tissue culture experiments, adiponectin increased the expression of iNOS, and production of nitric oxide, interleukin-6 (IL6) and MMP-3 in human OA cartilage. The effects of adiponectin of NO and IL-6 production were mediated through MAP kinases Erk1/2, p38 and JNK, and p38 pathway was involved in the adiponectin-induced MMP-3 production. Conclusions: Circulating adiponectin concentrations correlated positively with the measured biomarkers of cartilage degradation, i.e. COMP and MMP-3 in male OA patients; and adiponectin was found to increase the production of catabolic/proinflammatory mediators MMP-3, nitric oxide and IL-6 in human OA cartilage. The findings introduce adiponectin as a catabolic factor in OA.