Adipokines induce catabolism of newly synthesized matrix in cartilage and meniscus tissues

ABSTRACT

Purpose: Altered synovial levels of various adipokines (factors secreted by fat as well as other tissues) have been associated with osteoarthritis (OA) onset and progression. However, the metabolic effects of adipokines on joint tissues, in particular the fibrocartilaginous menisci, are not well understood. This study investigated effects of several adipokines on release of recently synthesized extracellular matrix in bovine cartilage and meniscus tissue explants. Materials and methods: After labeling newly synthesized proteins and sulfated glycosaminoglycans (sGAGs) with ³H-proline and ³⁵S-sulfate, respectively; bovine cartilage and meniscus tissue explants were cultured for 6 days in basal medium (control) or media supplemented with adipokines (1 µg/ml of leptin, visfatin, adiponectin, or resistin) or 20 ng/ml interleukin-1 (IL-1). Release of radiolabel and sGAG to the media during culture and the final explant water, DNA, sGAG, and retained radiolabel were measured. Matrix metalloproteinase (MMP-2) and MMP-3 activities were assessed using gelatin and casein zymography, respectively. Results: Water and DNA contents were not significantly altered by any treatment. Visfatin, adiponectin, resistin, and IL-1 stimulated sGAG release from meniscus, whereas only IL-1 stimulated sGAG release from cartilage. Release of ³H and ³⁵S was stimulated not only by resistin and IL-1 in meniscus but also by IL-1 in cartilage. Retained ³H was unaltered by any treatment, while retained ³⁵S was reduced by visfatin, resistin, and IL-1 in meniscus and by only IL-1 in cartilage. Resistin and IL-1 elevated active MMP-2 and total MMP-3 in meniscus, whereas cartilage MMP-3 activity was elevated by only IL-1. Conclusions: Resistin stimulated rapid and extensive catabolism of meniscus tissue, similar to IL-1, whereas adipokines minimally affected cartilage. Release of newly synthesized matrix was similar to overall release in both tissues. These observations provide further indications that meniscal tissue is more sensitive to pro-inflammatory factors than cartilage and also suggest further study of resistin’s role in OA.

KEYWORDS:

• Adipokines
• cartilage
• catabolism
• meniscus
• resistin

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Declaration of interest

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

Funding

This work was supported by a grant from the National Institutes of Health (NIAMS R01AR052861), and a National Science Foundation Graduate Research Fellowship (JFN).

Additional information

Funding

This work was supported by a grant from the National Institutes of Health (NIAMS R01AR052861), and a National Science Foundation Graduate Research Fellowship (JFN).