The Effects of Adipokines on Cartilage and Meniscus Catabolism

Abstract

Obesity is one of the primary risk factors for osteoarthritis. Increased adiposity is associated not only with alterations in joint loading, but also with increased systemic and joint concentrations of adipose tissue-derived cytokines, or “adipokines,” that promote a state of chronic, low-grade inflammation that may act in concert with other cytokines in the joint to increase joint degeneration. However, the direct effect of adipokines, such as leptin, visfatin, and interleukin-6 (IL-6), on joint tissues, such as articular cartilage and meniscus, are not fully understood. In this study, we examined the hypothesis that these adipokines act synergistically with interleukin-1 (IL-1) to increase catabolism and the production of proinflammatory mediators in cartilage and meniscus. Explants of porcine cartilage and meniscus were treated with physiologically relevant concentrations of leptin, IL-6, or visfatin, alone or in combination with IL-1. Visfatin and IL-1 promoted the catabolic degradation of both cartilage and meniscus, as evidenced by increased metalloproteinase activity, nitric oxide production, and proteoglycan release. However, leptin or IL-6 at physiologic concentrations had no effect on the breakdown of these tissues. These findings suggest that the effects of obesity-induced osteoarthritis may not be through a direct effect of leptin or IL-6 on cartilaginous tissues, but support a potential role for increased visfatin levels in this regard. These data provide an important first step in understanding the role of adipokines in regulating cartilage and meniscus metabolism; however, these adipokines may have different effects in the context of the whole joint and must be evaluated further.

Keywords:

• IL-1
• leptin
• IL-6
• visfatin
• matrix metalloproteinases
• adipokines

ACKNOWLEDGEMENTS

This study was supported by the Arthritis Foundation and NIH Grants AR50245, AG15768, AR48182, AR48852, and AR55434. We thank Poston Pritchett and Katherine Riera for technical assistance and Dr. Timothy Griffin for advice and expertise.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.