Fibroblast biology - Role of synovial fibroblasts in the pathogenesis of rheumatoid arthritis

There is growing evidence that activated synovial fibroblasts, as part of a complex cellular network, play an important role in the pathogenesis of rh eumatoid arthritis. In recent years, significant progress has been made in elucidating the specific features of these fibroblasts. It has been underst ood 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 co mplex pattern of molecular changes also maintained in the absence of extern al stimulation. This pattern of activation is characterized by alterations in the expression of regulatory genes and signaling cascades, as well as ch anges in pathways leading to apoptosis. These together result in the upregu lation of adhesion molecules that mediate the attachment of RA-SFs to the e xtracellular matrix and in the overexpression of matrix degrading enzymes t hat mediate the progressive destruction of the joints. In addition, activat ed RA-SFs exert specific effects on other cell types such as macrophages an d lymphocytes. While the initiating step in the activation of RA-SFs remain s elusive, several key pathways of RA-SF activation have been identified. H owever, 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 specifi c properties which together lead to their aggressive behavior.