Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis
Early structural changes in cartilage and bone are required for the attachment and invasion of inflamed synovial tissue during destructive inflammatory arthritis
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DOI：
10.1136/annrheumdis-2011-200386
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发表时间：
2012-06-01
影响因子：
27.4
通讯作者：
Redlich, Kurt
中科院分区：
文献类型：
--
作者：
Korb-Pap, Adelheid;Stratis, Athanasios;Redlich, Kurt
目的探讨类风湿性关节炎（RA）软骨细胞外基质降解的时间过程及细胞-基质相互作用对软骨细胞外基质降解的影响。使用RA小鼠模型分别分析血管翳附着于软骨和软骨破坏的时间过程，并将hTNFtg小鼠与白细胞介素（IL）-1（-/-）动物杂交，以研究IL-1在体内对这些TNF诱导机制的作用。此外，采用hTNFtg小鼠滑膜成纤维细胞（SF）和新鲜分离的关节软骨进行体外附着试验，以确定蛋白聚糖丢失在SF附着中的作用以及跨膜硫酸乙酰肝素蛋白聚糖syndecan-4的作用。结果hTNFtg小鼠体内分析表明，IL-1诱导的蛋白聚糖丢失先于这些过程，并构成这些过程的重要先决条件，在hTNFtg小鼠中，IL-1缺乏防止软骨蛋白聚糖的损失，并且几乎完全防止发炎的滑膜组织附着和随后侵入软骨。体外研究证实，软骨蛋白多糖的损失是所需的SF的附着和syndecan-4是显着参与SF的附着和activation.Conclusions本研究的结果表明，软骨蛋白多糖的损失是一个早期事件，在破坏性关节炎的过程中，促进附着的发炎滑膜，也启动基质降解和炎症，通过细胞增殖和炎症反应。矩阵相互作用
Objective To elucidate the mechanisms involved in cartilage damage in an experimental model of rheumatoid arthritis (RA) by specifically addressing the time course of extracellular matrix degradation and the contribution of cell-matrix interactions for initiation and perpetuation of this process.Methods The human tumour necrosis factor (TNF) transgenic (hTNFtg) mouse model of RA was used to analyse the time course of pannus attachment to the cartilage and cartilage destruction, respectively, and crossed hTNFtg mice with interleukin (IL)-1(-/-) animals were used to investigate the role of IL-1 on these TNF-induced mechanisms in vivo. In addition, an in vitro attachment assay using synovial fibroblasts (SFs) from hTNFtg mice and freshly isolated articular cartilage was used to determine the role of proteoglycan loss in attachment of SFs and the role of the transmembrane heparan sulfate proteoglycan syndecan-4.Results In vivo analyses of hTNFtg mice showed that proteoglycan loss induced by IL-1 precedes and constitutes an important prerequisite for these processes as, in hTNFtg mice, IL-1 deficiency protected from the loss of cartilage proteoglycans and almost completely prevented the attachment and subsequent invasion of inflamed synovial tissue into cartilage. In vitro studies confirmed that loss of cartilage proteoglycans is required for attachment of SFs and that syndecan-4 is prominently involved in SF attachment and activation.Conclusions The results of this study suggest that the loss of cartilage proteoglycans is an early event in the course of destructive arthritis that facilitates the attachment of the inflamed synovial membrane and also initiates matrix degradation and inflammation through cell-matrix interactions.