fibroblast biology role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis纤维母细胞生物学滑膜成纤维细胞在类风湿性关节炎的发病机制中的作用.pdfVIP

/content/2/5/361 Review Fibroblast biology Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis Thomas Pap, Ulf Müller-Ladner*, Renate E Gay and Steffen Gay University Hospital, Zürich, Switzerland, and *University of Regensburg, Germany Received: 6 January 2000 Arthritis Res 2000, 2:361–367 Accepted: 27 April 2000 Published: 8 June 2000 © Current Science Ltd (Print ISSN 1465-9905; Online ISSN 1465-9913) Abstract There is growing evidence that activated synovial fibroblasts, as part of a complex cellular network, play an important role in the pathogenesis of rheumatoid arthritis. In recent years, significant progress has been made in elucidating the specific features of these fibroblasts. It has been understood that although macrophage and lymphocyte secreted factors contribute to their activation, rheumatoid arthritis synovial fibroblasts (RA-SFs) do not merely respond to stimulation by pro-inflammatory cytokines, but show a complex pattern of molecular changes also maintained in the absence of external stimulation. This pattern of activation is characterized by alterations in the expression of regulatory genes and signaling cascades, as well as changes in pathways leading to apoptosis. These together result in the upregulation of adhesion molecules that mediate the attachment of RA-SFs to the extracellular matrix and in the overexpression of matrix degrading enzymes that mediate the progressive destruction of the joints. In addition, activated RA-