Regulation of Apoptosis in Rheumatoid Synoviocytes

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by early synovitis following synovial proliferation and infiltration of various inflammatory cells (1,2). The process of disease progression, characterized by activation and hyperplasia of synoviocytes, mainly of synovial fibroblasts, results in cartilage and bone destruction (1,2). Proliferation of synoviocytes is, however, not limitless, and spontaneous remission or arrest of synovial proliferation are occasionally observed(3,4). First, our laboratories following by others have demonstrated that RA synoviocytes express functional Fas antigen (CD95/APO-1) and that these cells undergo Fas-mediated apoptosis both either in vivo and in vitro (5–8). These findings suggest that Fas-mediated apoptosis may play a critical role in the regression of synovial hyperplasia in RA. It also implies that induction of intractable synovial hyperplasia in RA may occur when Fas-mediated apoptosis ceases to operate partially or completely leading to accumulation of Fas-positive proliferating synoviocytes. However, the regulatory mechanisms that control apoptosis are not well understood. Identification of the regulatory mechanisms in RA synoviocytes may provide important insights into not only understanding of the pathophysiology of RA but also the development of novel strategies for RA therapy. In this chapter, current of the study by our laboratory on the regulatory mechanisms of Fas-mediated apoptosis in RA was described. We also propose a novel gene therapy strategy in the treatment of RA based on induction of the apoptosis gene synovectomy in patients with RA.