High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis
High molecular weight hyaluronic acid down-regulates the gene expression of osteoarthritis-associated cytokines and enzymes in fibroblast-like synoviocytes from patients with early osteoarthritis
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DOI：
10.1016/j.joca.2006.05.009
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发表时间：
2006-12-01
影响因子：
7
通讯作者：
Hou, S. -M.
中科院分区：
文献类型：
--
作者：
Wang, C. -T.;Lin, Y. -T.;Hou, S. -M.
目的：活化的滑膜细胞在人类骨关节炎（OA）的发生发展中起重要作用。关节内注射高分子量透明质酸（HMW-HA）已被用作膝CA的粘滞补充剂，但其对滑膜细胞的影响尚未公开。本研究旨在研究HMW-HA对16种OA相关细胞因子和酶基因表达的影响，包括白细胞介素（IL）-1 β、IL-6、IL-8、白血病抑制因子（LIF）、肿瘤坏死因子（TNF）-α、TNF-α转化酶（TACE）、基质金属蛋白酶（MMP）-1、MMP-2、MMP-3、MMP-9、MMP-13、金属蛋白酶组织抑制剂（TIMP）-1、TIMP-2、聚集蛋白聚糖酶-1、聚集蛋白聚糖酶-2和诱导型一氧化氮合酶（iNOS）在早期OA患者成纤维样滑膜细胞（FLS）中的表达。从15例早期OA患者的膝关节中获得滑液来源的FLS。用或不用600-800 kDa HMW-HA处理IL-1刺激或未刺激的FLS。此外，使用抗CD 44单克隆抗体（mAb）的阻断实验来检查CD 44在HMW-HA效应中的参与。我们设计并验证了实时定量聚合酶链反应（Q-PCR）与SYBR绿色染料的同时定量的16个基因的expression.Results：HMW-HA下调IL-8和iNOS基因的表达在未刺激的FLS和下调聚集蛋白聚糖酶-2和TNF-α基因的表达在IL-1刺激的FLS。结论：HMW-HA可能通过下调FLS中聚集蛋白聚糖酶-2的表达，对CA具有结构修饰作用。HMW-HA还通过下调FLS中的TNF-α、IL-8和iNOS而具有抗炎作用。这些作用可能通过CD 44和HMW-HA的相互作用介导。(C)2006年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: Activated synoviocytes play important roles in the progression of human osteoarthritis (OA). Intra-articular injection of high molecular weight hyaluronic acid (HMW-HA) has been used as viscosupplementation for knee CA but its effect on synoviocytes remains undisclosed. This study aims to investigate the effects of HMW-HA on the gene expression of 16 OA-associated cytokines and enzymes, including interleukin (IL)-1 beta, IL-6, IL-8, leukemia inhibitory factor (LIF), tumor necrosis factor (TNF)-alpha, TNF-alpha converting enzyme (TACE), matrix metalloproteinase (MMP)-1, MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, aggrecanase-1, aggrecanase-2, and inducible nitric oxide synthase (iNOS), in fibroblast-like synoviocytes (FLS) from patients with early stage OA.Method. Synovial fluid-derived FLS were obtained from the knees of 15 patients with early stage OA. IL-1-stimulated or unstimulated FLS were cultured with or without the treatment of 600-800 kDa HMW-HA. Moreover, blocking experiments with anti-CD44 monoclonal antibodies (mAb) were used to examine the involvement of CD44 in HMW-HA effects. We designed and validated the real-time quantitative polymerase chain reaction (Q-PCR) assays with SYBR Green dyes for simultaneous quantification of the expression of the 16 genes.Results: HMW-HA down-regulated IL-8 and iNOS gene expression in unstimulated FLS and down-regulated aggrecanase-2 and TNF-alpha gene expression in IL-1-stimulated FLS. CD44 blocking inhibited the down-regulatory effects of HMW-HA on gene expression.Conclusion: HMW-HA may have a structure-modifying effect for CA by down-regulation of aggrecanase-2 in FLS. HMW-HA also has an anti-inflammatory effect by down-regulation of TNF-alpha, IL-8, and iNOS in FLS. These effects may be mediated through the interaction of CD44 and HMW-HA. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.