Suppressive Activity of Chondroitin Sulfate on Periostin Production by Synoviocytes from Knee Osteoarthritis In Vitro

Daisuke Tamaki, S. Ishikawa, A. Yamada, Amane Otaki, K. Asano
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Abstract

Background: Knee osteoarthritis (OA) is well known to be one of the most common joint disease in elderly people and characterized by pain, stiffness and loss of function in articulating joints, which develop slowly and worsen over time. Chondroitin sulfate (CS) and glucosamine hydrochloride are used for the treatment of OA and reported that these substances are favorably modify the clinical symptoms, especially pain, however, the therapeutic mechanisms of these substances are not fully understood. The present study was undertaken to examine the influence of CS on the production of periostin, which is one of the important molecules associated with OA development, by synoviocytes from an OA patient by an in vitro cell culture technique. Methods: Synoviocytes (1 x 105 cell/ml) were stimulated with 10.0 ng/ml IL-13 in the presence of various concentrations of CS. After 48 h, periostin content in culture supernatants was examined by ELISA. We also examined the influence of CS on transcription factor, STAT6, activation and periostin mRNA expression in synoviocytes 12 and 24 h after IL-13 stimulation, respectively. Results: Addition of CS into cell cultures caused the suppression of periostin production from synoviocytes induced by IL-13 stimulation through the inhibition of STAT6 activation and periostin mRNA expression. The minimum concentration of CS that caused significant suppression of periostin production, STAT6 activation and mRNA expression was 10.0 μg/ml. Conclusion: These results strongly suggest that the ability of CS to suppress periostin production from synoviocytes may account, at least in part, for the clinical efficacy of CS on OA.
硫酸软骨素对膝关节骨性关节炎滑膜细胞生成骨膜素的抑制作用
背景:膝关节骨性关节炎(OA)是老年人最常见的关节疾病之一,以关节疼痛、僵硬和功能丧失为特征,其发展缓慢且随时间恶化。硫酸软骨素(CS)和盐酸氨基葡萄糖用于骨性关节炎的治疗,并报道这些物质有利于改善临床症状,特别是疼痛,但这些物质的治疗机制尚不完全清楚。本研究通过体外细胞培养技术研究了CS对骨髓炎患者滑膜细胞产生骨膜蛋白的影响,骨膜蛋白是骨髓炎发生的重要分子之一。方法:在不同浓度的CS存在下,用10.0 ng/ml IL-13刺激滑膜细胞(1 × 105细胞/ml)。48h后,用ELISA法检测培养上清中的骨膜蛋白含量。我们还分别检测了CS在IL-13刺激后12和24 h对滑膜细胞转录因子、STAT6、激活和骨膜蛋白mRNA表达的影响。结果:CS通过抑制STAT6激活和骨膜蛋白mRNA表达,抑制IL-13刺激诱导的滑膜细胞产生骨膜蛋白。CS对骨膜蛋白生成、STAT6激活和mRNA表达的最低抑制浓度为10.0 μg/ml。结论:这些结果强烈表明,CS抑制滑膜细胞产生骨膜蛋白的能力可能至少部分解释了CS治疗OA的临床疗效。
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