脂联素促进骨关节炎滑膜细胞PGE_2合成及其机制的初步研究

Adiponectin promotes the synthesis of PGE_2 in synovial fibroblasts in the patients with osteoarthritis: a preliminary study on the mechanism

背景:骨关节炎患者关节液中存在着高水平的脂联素,且研究表明脂联素与骨关节炎的发生和发展有着密切联系。目的:本文旨在探讨脂联素对骨关节炎滑膜细胞前列腺素E2(PGE2)产生的影响,并对其机制做初步的研究。方法:收集骨关节炎患者滑膜组织行细胞培养,观察给予不同浓度脂联素和脂联素刺激不同时间后PGE2的合成情况;比较脂联素刺激18h后,PGE2合成相关因子环氧合酶(COX)-1、COX-2、胞浆型前列腺素E合成酶(cPGES)、膜相关型前列腺素E合成酶(mPGES)-1、mPGES-2基因的表达。结果:脂联素能呈浓度依赖性的促进骨关节炎滑膜细胞PGE2的合成,这种效应在18h达到高峰;脂联素能显著增强骨关节炎滑膜细胞COX-2和mPGES-1mRNA的表达,但对COX-1、cPGES、mPGES-2作用不明显。结论:脂联素能通过COX-2和mPGES-1依赖性的促进PGE2的合成,脂联素在骨关节炎发病中可能扮演着前炎性因子的角色。

Background： There is a high level of adiponectin in the synovial fluid of patients with osteoarthritis. Previous studies had shown that the occurrence and development of osteoarthritis were closely correlated with adiponectin. Objective： This study is to evaluate the effect of adiponectin on the synthesis of prostaglandin E2 （PGE2） in synovial fibroblasts in the patients with osteoarthritis and do a preliminary study on the mechanism. Methods： Synovial membranes were collected from 8 patients with osteoarthritis for cell culture. The synthesis of PGE2 was observed at different concentrations of adiponectin and adiponectin stimulation in different time. The gene expression of relevant factors to the synthesis of PGE2, such as cyclooxygenase （COX）-1, COX-2, cytosolic prostaglandin E synthase （cPGES）, microsomal prostaglandin E synthase （mPGES）-1 and mPGES-2 were detected at 18 h after adiponectin stimulation. Results： Adiponectin induced the production of PGE2 in a concentration-dependent manner, which reached the peak at 18 h after adiponectin stimulation. Adiponectin could significantly enhance the expression of COX-2 and mPGES-1 mRNA, whereas COX-1, cPGES and mPGES-2 mRNA levels were unchanged. Conclusions： Adiponectin can promote PGE2 synthesis in synovial fibroblasts through the COX-2 and mPGES-1 pathway. Adiponectin may play a role of pro-inflammatory factor in the pathogenesis of osteoarthritis.