脂联素受体 1 介导脂联素诱导的类风湿关节炎和骨关节炎滑膜成纤维细胞前列腺素 E2 产生的差异。

Adiponectin receptor 1 mediates the difference in adiponectin- induced prostaglandin E2 production in rheumatoid arthritis and osteoarthritis synovial fibroblasts.

机构信息

Department of Orthopedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

出版信息

Chin Med J (Engl). 2011 Dec;124(23):3919-24.

PMID:22340319

Abstract

BACKGROUND

The synovial fluid concentrations of adiponectin are significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA). Accumulating evidence suggests that adiponectin may be an inducer of inflammation in arthritis, but the mechanism remains unclear. The objectives of this study were to compare the expression levels of adiponectin receptors in rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF), evaluate the roles of adiponectin receptors in adiponectin-induced prostaglandin E(2) (PGE(2)) production, and then investigate the effects of a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX)-2-selective inhibitor on adiponectin-induced PGE(2) release.

METHODS

The expressions of adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA and protein in synovial fibroblasts from seven patients with RA and eight patients with OA undergoing total knee replacement were evaluated by real-time polymerase chain reaction, immunofluorescence microscopy and Western blotting analysis. Adiponectin-induced PGE(2) production was detected by enzyme-linked immunosorbent assay. RNA interference against the AdipoR1 and AdipoR2 genes was performed to investigate the effects of the adiponectin receptors on adiponectin-induced PGE(2) production in both RASF and OASF.

RESULTS

AdipoR1 and AdipoR2 mRNA and protein were expressed by both RASF and OASF. Compared with OASF, RASF exhibited higher levels of AdipoR1, but there was no significant difference for AdipoR2. Adiponectin induced the production of PGE(2) by the synovial fibroblasts in a concentration-dependent manner, and this was more obvious in RASF. RNA interference showed that the difference may be mediated by the diverse distribution of AdipoR1. The adiponectin-induced PGE(2) production was efficiently relieved by the NSAID and COX-2-selective inhibitor.

CONCLUSION

The present findings suggest that AdipoR1 may mediate the difference in adiponectin-induced PGE(2) production in RASF and OASF.

摘要

背景

滑液中脂联素浓度在类风湿关节炎（RA）患者中明显高于骨关节炎（OA）患者。越来越多的证据表明脂联素可能是关节炎中的一种炎症诱导物，但机制尚不清楚。本研究的目的是比较类风湿关节炎滑膜成纤维细胞（RASF）和骨关节炎滑膜成纤维细胞（OASF）中脂联素受体的表达水平，评估脂联素受体在脂联素诱导的前列腺素 E2（PGE2）产生中的作用，然后研究非甾体抗炎药（NSAID）和环氧化酶（COX）-2 选择性抑制剂对脂联素诱导的 PGE2 释放的影响。

方法

通过实时聚合酶链反应、免疫荧光显微镜和 Western 印迹分析评估来自 7 名接受全膝关节置换术的 RA 患者和 8 名 OA 患者的滑膜成纤维细胞中脂联素受体 1（AdipoR1）和 AdipoR2 mRNA 和蛋白的表达。通过酶联免疫吸附试验检测脂联素诱导的 PGE2 产生。通过 RNA 干扰针对 AdipoR1 和 AdipoR2 基因，研究脂联素受体对 RASF 和 OASF 中脂联素诱导的 PGE2 产生的影响。

结果

RASF 和 OASF 均表达 AdipoR1 和 AdipoR2 mRNA 和蛋白。与 OASF 相比，RASF 表现出更高水平的 AdipoR1，但 AdipoR2 没有显着差异。脂联素以浓度依赖的方式诱导滑膜成纤维细胞产生 PGE2，在 RASF 中更为明显。RNA 干扰表明，这种差异可能是由 AdipoR1 的不同分布介导的。非甾体抗炎药和 COX-2 选择性抑制剂可有效缓解脂联素诱导的 PGE2 产生。