Resveratrol (RES) has a protective effect on osteoarthritis (OA), nevertheless, the underlying mechanisms of RES towards obesity-related OA are still unclear. This study is aimed to determine whether leptin resistant mechanism presents in articular cartilage of obesity-related OA and whether the protective effect of RES is involved in the regulation of leptin signal by affecting suppressor of cytokine signaling 3 (SOCS3). Male C57BL/6 J mice were fed with standard chow diet, high fat diet (HFD) or high fat diet with RES (45 mg/kg.bw) for 22 weeks. Knee joints of mice were evaluated by histological and immunohistochemistry analysis. Serum level of leptin was measured by ELISA. The leptin, leptin receptor (OB-Rb), SOCS3 mRNA expression and JAK2, STAT3, OB-Rb and SOCS3 protein expression in cartilage were determined by real-time RT-PCR and western blot. In addition, SW1353 cells were pretreated with or without AG490, and stimulated with leptin in the presence or absence of RES to detect JAK2, STAT3, matrix metalloproteinase-13 (MMP-13) and SOCS3 expression. We found that HFD could induce obesity-related OA and RES prevented its progression. Serum leptin and mRNA expression in cartilage was up-regulated by HFD, while RES ameliorated the elevation. Besides, RES significantly inhibited the JAK2/STAT3 signaling pathway in cartilage, as well as SOCS3. In in vitro study, RES exhibited the same effect in SW1353 cells which stimulated with leptin. In conclusion, no significant leptin resistance existed in cartilage of obesity-related OA and the inhibitory effect of RES on obesity-related OA via alleviating JAK2/STAT3 signaling pathway is independent of SOCS3.

中文翻译：

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白藜芦醇通过减轻JAK2 / STAT3信号通路对肥胖相关性骨关节炎的保护作用独立于SOCS3。

白藜芦醇（RES）对骨关节炎（OA）有保护作用，但是，RES对肥胖相关OA的潜在机制仍不清楚。本研究旨在确定肥胖相关OA的关节软骨中是否存在瘦素抵抗机制，以及RES的保护作用是否通过影响细胞因子信号传导3（SOCS3）的抑制因子参与瘦素信号的调节。给雄性C57BL / 6 J小鼠喂食标准食物，高脂饮食（HFD）或高脂饮食以及RES（45 mg / kg.bw），持续22周。通过组织学和免疫组织化学分析评估小鼠的膝关节。通过ELISA测量血清瘦素水平。瘦素，瘦素受体（OB-Rb），SOCS3 mRNA表达和JAK2，STAT3，通过实时RT-PCR和western blot检测软骨中OB-Rb和SOCS3蛋白的表达。此外，在有或没有AG490的情况下，对SW1353细胞进行预处理，然后在有或没有RES的情况下用瘦蛋白刺激SW1353细胞，以检测JAK2，STAT3，基质金属蛋白酶-13（MMP-13）和SOCS3的表达。我们发现，HFD可能诱发肥胖相关的OA，而RES阻止了其进展。血清瘦素和mRNA在软骨中的表达被HFD上调，而RES改善了这一水平。此外，RES显着抑制软骨以及SOCS3的JAK2 / STAT3信号通路。在体外研究中，RES在瘦蛋白刺激的SW1353细胞中表现出相同的作用。综上所述，