Role of Synovial Fibroblasts in Rheumatoid Arthritis

Lee, Sang Heon

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial tissue proliferation with progressive joint destruction. The etiology of RA remains unknown, but many factors, including autoimmunity, cytokines and genetic factors, participate in its pathogenesis. There is growing evidence that activated fibroblast like synoviocytes (FLS), as part of a complex cellular network, play an important role in the pathogenesis of RA. It has been understood that proinflammatory cytokines secreted from macrophages and lymphocytes may influence the activation of FLS, but invasive and aggressive behaviour of RA-FLS maintained even in the absence of inflammatory stimuli. This kind of partial transformation is characterized by alterations in the expression of regulatory genes such as p53 and signaling cascade, as well as changes in pathway leading to apoptosis. Under the influences of proinflammatory cytokines in rheumatoid joints, RA-FLS is actively involved in the matrix degradation through the production of matrix metalloproteinases (MMP) and cathepsin. In addition, activated RA-FLS exert specific effects on other cell types such as macrophages and lymphocytes. While careful mapping of cytokine networks a decade ago led to the successful development of anti-cytokine therapy, the elucidation of gene mutations and detailed signaling transduction pathways that are specific to RA as well as mechanisms of action of MMP may provide the new targets for novel therapeutic interventions for RA.