Mechanism Of Adipokines-visfatin And Adiponectin In Osteoarthritis

Objective 1. To analyze the distribution of visfatin between plasma and synovial fluid (SF) of patients with osteoarthritis (OA) and normal subjects, identify the role of visfatin in OA.2. Focus on the effects of adiponectin on the chondrocytes in OA.Methods Levels of visfatin were measured by a sandwich enzyme-linked immunosorbent assay in plasma and SF collected from 30 female OA patients and 12 normal subjects. Degradation markers of cartilage matrix in SF were also measured. The severity of OA was determined according to the Kellgren and Lawrence classification. Correlation analyses between visfatin and degradation markers or OA severity were performed. Immunofluorescence, Real-time PCR, western blotting techniques were evaluated for the difference of adiponectin receptors expression between OA chondrocytes and normal chondrocytes; OA chondrocytes were stimulated with some inhibitors; effects of adiponectin on niric oxide synthesis in OA chondrocytes were observed in vitro.Results Compared to controls, OA patients had higher SF visfatin concentration (8.95±2.5 vs.4.48±2.49 ng/ml, P< 0.001). Plasma visfatin levelswere higher inOApatients than those in control subjects, but not statistical significance (5.37±1.45 vs. 4.93±1.4 ng/ml, P= 0.466). SF visfatin positively correlated with degradation biomarker of collagenⅡ, CTX-Ⅱ(r= 0.497, P= 0.005), and degradation biomarker of aggrecan, AGG1 (r=0.451, P=0.012) and AGG2 (r= 0.434, P=0.017). We compared the expression of adiponectin receptors in primary chondrocytes from OA patients and normal subjects, but compared to normal chondrocytes, the three adiponectin receptors were down-regulated in osteoarthritic chondrocytes, especially AdipoRl. In vitro experiments confirmed that adiponectin can activate the transcriptional activity of NF-κB, enhance promoter region of iNOS transcription, lead to increased expression of iNOS protein, and OA chondrocytes synthesed a large number of NO. In addition, adiponectin is able to increase IL-6, TNF-α, MMP-3, MMP-9 and TIMP-2 by cultured OA chondrocytes in vitro, whereas it was unable to modulate IL-1β, MCP-1, PGE2, TIMP-1 and MMP-13 release.Conclusion 1. visfatin is a new discovery of another adipokines, regulating the degradation of cartilage matrix in OA.2. Adiponectin can release certain inflammatory cytokines and cartilage matrix metabolism molecules by OA chondrocytes, may be a proinflammatory factor, had an important role in the pathogenesis of OA. These results suggest that fat-derived adipokines have an important role in the metabolism of OA.