Resistin as a factor in osteoarthritis: synovial fluid resistin concentrations correlate positively with interleukin 6 and matrix metalloproteinases MMP-1 and MMP-3

Abstract

Objectives: Resistin is an adipocytokine that has been related to inflammation and insulin resistance. Following knee injury, elevated levels of resistin have been found in synovial fluid (SF) while very little is known about the role of resistin in osteoarthritis (OA). The aim of the present study was to investigate resistin levels in OA joints and to determine if it is associated with inflammatory and catabolic factors in the joints.

Method: SF, plasma, and cartilage samples were collected from 88 OA patients undergoing knee replacement surgery. Resistin levels were measured by enzyme-linked immunosorbent assay (ELISA) in SF, plasma, and cartilage culture media.

Results: Significant levels of resistin [0.75 (0.67) ng/mL; median (IQR)] were found in SF from OA patients. Resistin correlated positively with interleukin (IL)-6 (r = 0.39, p < 0.001) and with matrix metalloproteinases MMP-1 (r = 0.31, p = 0.004) and MMP-3 (r = 0.24, p = 0.024) in SF. Resistin was also released from cultured OA cartilage and it correlated with resistin levels in SF (r = 0.39, p < 0.001). In addition, resistin levels in plasma correlated positively with those in SF (r = 0.44, p < 0.001). There were no differences in SF or plasma resistin concentrations between females and males or between non-diabetic and diabetic patients, and resistin did not correlate with body mass index (BMI).

Conclusions: Resistin is present in OA joints and is released from OA cartilage. Levels of resistin in SF are associated with inflammatory and catabolic factors, suggesting that resistin has a role to play in the pathogenesis of, and as a possible drug target in, OA.

Acknowledgements

The excellent technical assistance of M Kukkonen, E Jaakkola, P Miikkulainen, and E Lehto, and the skillful secretarial help of H Määttä are greatly acknowledged. This study was financially supported by the Academy of Finland, the Competitive Research Funding of the Pirkanmaa Hospital District, the Päivikki and Sakari Sohlberg Foundation, and the Scandinavian Rheumatology Research Foundation. AK is a student in the Tampere Graduate Programme in Biomedicine and Biotechnology.