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首页> 外文期刊>Osteoarthritis and cartilage >Glatiramer acetate (GA), the immunomodulatory drug, inhibits inflammatory mediators and collagen degradation in osteoarthritis (OA) cartilage.
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Glatiramer acetate (GA), the immunomodulatory drug, inhibits inflammatory mediators and collagen degradation in osteoarthritis (OA) cartilage.

机译：醋酸格拉替雷（GA）是一种免疫调节药物，可抑制骨关节炎（OA）软骨中的炎症介质和胶原蛋白降解。

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OBJECTIVE: Glatiramer acetate (GA), the generic name for Copaxone, an immunomodulatory agent, has been shown to induce interleukin-1 receptor antagonist (IL-1Ra) production in macrophages. We therefore tested the effects of GA on the catabolic activities of osteoarthritis (OA) chondrocytes. DESIGN: Primary human chondrocytes and OA cartilage explants were utilized in this study. IL-1Ra, pro-matrix metalloproteinase-13 (proMMP-13) and prostaglandin E(2) (PGE(2)) were estimated in the cell culture supernatants and in vitro MMP-13 activity was measured using fluorogenic substrate. TaqMan Real-Time quantitative polymerase chain reaction (RT-qPCR) was performed to estimate relative expression levels of genes. RESULTS: GA treatment significantly increased transcription and production of sIL-1Ra (P=0.001) in both culture models. Furthermore, addition of GA (100 mug) inhibited: (1) spontaneous collagen degradation as assayed by CTX II enzyme-linked immunosorbent assay (ELISA) [mean CTX II (ng/g cartilage)] in control was 7.79 [95% confidence interval (CI) 2.57-13.02]-3.415 (95% CI 0.81-6.02) (P=0.0286); (2) spontaneous proMMP-13 secretion [mean MMP-13 (ng/g cartilage)] in control was 16.98 (95% CI 7.739-26.23)-6.973 (95% CI 1.632-12.31) (P=0.0286); (3) production of IL-1beta-induced inflammatory mediators such as nitric oxide (NO) [mean NO (muM)] in IL-1 cultures was 11.47 (95% CI 7.10-15.83)-0.87 (95% CI 0.18-1.56) (P=0.0022); and (4) recombinant MMP-13 in vitro activity (15-25%; P=0.004). CONCLUSIONS: These data suggest that GA effects may be due to upregulation of IL-1Ra as well as direct inhibition of MMP-13 activity. Based on these studies, we propose that GA has potential for disease modifying properties in OA and should be evaluated in vivo in animal studies.
机译：目的：醋酸格拉替雷（GA）是一种免疫调节剂Copaxone的总称，已被证明可诱导巨噬细胞中白介素1受体拮抗剂（IL-1Ra）的产生。因此，我们测试了GA对骨关节炎（OA）软骨细胞分解代谢活性的影响。设计：本研究利用原代人软骨细胞和OA软骨外植体。在细胞培养上清液中估计IL-1Ra，前基质金属蛋白酶13（pr​​oMMP-13）和前列腺素E（2）（PGE（2）），并使用荧光底物测量体外MMP-13活性。进行TaqMan实时定量聚合酶链反应（RT-qPCR）以估计基因的相对表达水平。结果：在两种培养模型中，GA处理均显着提高了sIL-1Ra的转录和产量（P = 0.001）。此外，添加GA（100马克杯）会抑制：（1）对照中CTX II酶联免疫吸附测定（ELISA）[平均CTX II（ng / g软骨）]测定的自发性胶原蛋白降解为7.79 [95％置信区间（CI）2.57-13.02] -3.415（95％CI 0.81-6.02）（P = 0.0286）; （2）对照中自发的proMMP-13分泌[平均MMP-13（ng / g软骨）]为16.98（95％CI 7.739-26.23）-6.973（95％CI 1.632-12.31）（P = 0.0286）; （3）IL-1培养物中IL-1beta诱导的炎性介质如一氧化氮（NO）[平均NO（muM）]的产生为11.47（95％CI 7.10-15.83）-0.87（95％CI 0.18-1.56） ）（P = 0.0022）; （4）重组MMP-13的体外活性（15-25％; P ＝ 0.004）。结论：这些数据表明GA作用可能是由于IL-1Ra的上调以及对MMP-13活性的直接抑制。基于这些研究，我们建议GA在OA中具有改善疾病的潜力，应在动物研究中对其进行体内评估。

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