Korb A, Peters M, Meinecke I, Pap T
Bereich molekulare Medizin des Muskuloskelettalen Systems, Universitätsklinikum Münster, Domagkstrasse 3, 48129 Münster.
Z Rheumatol. 2007 Jul;66(4):311-6. doi: 10.1007/s00393-007-0181-5.
Rheumatoid arthritis (RA) is a chronic autoimmune disease of still unknown etiology that results in characteristic destructive changes of the joints. Research of the past years has demonstrated that synovial fibroblasts play a central role in the initiation and perpetuation of these destructive changes. Stimulation of the synovial fibroblasts through complex and interacting intracellular signaling pathways results in a stable activation that is maintain even without continuous stimulation by inflammatory cells and their mediators. The pathological attachment to articular cartilage, increased secretion of matrix degrading enzymes and alterations in programmed cell death are main characteristics of synovial fibroblasts from patients with RA and result in the progressive destruction of articular structures. The permanent activation of a number of intracellular signaling pathways constitutes the underlying responsible mechanism for the activation of synovial fibroblasts in RA. These signaling pathways do not only show a high degree of complexity, but are also interconnected in multiple ways. This article summarizes recent findings on the activation of intracellular signaling pathways in fibroblasts and points to potential targets for novel therapeutic strategies.
类风湿关节炎（RA）是一种病因仍不明的慢性自身免疫性疾病，会导致关节出现特征性的破坏性改变。过去几年的研究表明，滑膜成纤维细胞在这些破坏性改变的起始和持续过程中起核心作用。通过复杂且相互作用的细胞内信号通路刺激滑膜成纤维细胞会导致一种稳定的激活状态，即使在没有炎症细胞及其介质持续刺激的情况下也能维持。对关节软骨的病理性附着、基质降解酶分泌增加以及程序性细胞死亡的改变是RA患者滑膜成纤维细胞的主要特征，并导致关节结构的渐进性破坏。多种细胞内信号通路的持续激活构成了RA中滑膜成纤维细胞激活的潜在负责机制。这些信号通路不仅表现出高度的复杂性，而且还以多种方式相互连接。本文总结了成纤维细胞内信号通路激活的最新研究结果，并指出了新型治疗策略的潜在靶点。
