Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis
- PMID: 11094449
- PMCID: PMC130137
- DOI: 10.1186/ar113
Fibroblast biology. Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis
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-SFs exert specific effects on other cell types such as macrophages and lymphocytes. While the initiating step in the activation of RA-SFs remains elusive, several key pathways of RA-SF activation have been identified. However, there is so far no single, specific marker for this phenotype of RA-SF. It appears that activated RA-SFs are characterized by a set of specific properties which together lead to their aggressive behavior.
Figures
References
-
- Firestein GS. Invasive fibroblast-like synoviocytes in rheumatoid arthritis. Passive responders or transformed aggressors? Arthritis Rheum. 1996;39:1781–1790. - PubMed
-
- Pap T, Franz JK, Gay RE, Gay S. Has research on lymphocytes hindered progress in rheumatoid arthritis? In Challenges in Rheumatoid Arthritis Edited by Bird H, Snaith M Oxford: Blackwell Science; 1999.
-
- Franz JK, Pap T, Müller-Ladner U, Gay RE, Burmester GR, Gay S. T-cell independent joint destruction. . In T Cells in Arthritis Edited by Miossec P, van-den BW, Firestein GS Basel: Birkenhäuser, 1998. pp. 55–74.
-
- Fassbender HG. Histomorphological basis of articular cartilage destruction in rheumatoid arthritis. . Coll Relat Res. 1983;3:141–155. - PubMed
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical