Role of synovial fibroblasts in rheumatoid arthritis.
Role of synovial fibroblasts in rheumatoid arthritis.
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DOI：
10.2174/1381612820666140825122036
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发表时间：
2014-12
影响因子：
3.1
通讯作者：
S. Lefèvre;F. Meier;E. Neumann;U. Muller-Ladner
中科院分区：
文献类型：
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作者：
S. Lefèvre;F. Meier;E. Neumann;U. Muller-Ladner
类风湿性关节炎（RA）是最常见的自身免疫性关节疾病。其特征在于慢性炎症和进行性关节破坏。由于研究传统上集中在免疫细胞和细胞因子上，基质细胞的作用仅在有限程度上得到解决。然而，类风湿性滑膜内的细胞-细胞相互作用改变了滑膜成纤维细胞（SF）的表型，其如今被认为是RA破坏过程中的活跃和侵袭性驱动因素。SF主动附着并侵入关节软骨，从而表达增加量的粘附分子和促炎和基质降解介质。此外，RASF通过释放促血管生成因子刺激滑膜血管形成。因此，血管生成支持免疫细胞流入受影响的关节，从而使炎症过程永久化，并促进RASF进入血流，从而促进RA的传播。尽管深入研究，早期病理生理过程仍然在很大程度上未知。在这方面，RA的关节炎前期进行了讨论。早期和强化治疗被认为是非常有效的，有利于长期的结果。然而，尽管创新疗法和改进的治疗策略被应用于实现临床缓解，但对疗法的失败或仅部分响应仍然很常见。鉴于目前批准的治疗方法都没有靶向RASF，因此有必要对新策略进行深入研究。在这篇综述中，新的发现，导致改变成纤维细胞表型在RA进行性炎症和破坏方面进行了讨论。潜在的新的治疗概念也得到了解决。
Rheumatoid arthritis (RA) is the most common autoimmune articular disorder. It is characterized by chronic inflammation and progressive joint destruction. As research traditionally focused on immune cells and cytokines, the role of stromal cells was addressed only to a limited extent. However, cell-cell interactions within the rheumatoid synovium alter the phenotype of synovial fibroblasts (SFs), which are nowadays considered as active and aggressive drivers in the destructive process of RA. SFs actively attach to and invade articular cartilage, thereby expressing increased amounts of adhesion molecules and proinflammatory and matrix-degrading mediators. Furthermore, RASFs stimulate synovial vascularization through the release of proangiogenic factors. As a result, angiogenesis supports the influx of immune cells into affected joints, thereby perpetuating inflammatory processes, and facilitates access of RASFs to the bloodstream, thus boosting dissemination of RA. Despite intensive research, early pathophysiological processes still remain largely unknown. In this respect, a prearthritic phase of RA is discussed. Early and intensive therapy is considered to be very effective and beneficial for long-term outcome. However, although innovative therapy and improved treatment strategies are applied to achieve clinical remission, failure of or only partial response to therapy remains common. Given that none of the currently approved therapies target RASFs, intensive research into new strategies is warranted. In this review, novel findings leading to the altered fibroblast phenotype in RA are discussed in terms of progressive inflammation and destruction. Potential novel therapeutic concepts are also addressed.