THE ROLE OF DKK1 IN RHEUMATOID ARTHRITIS

Abstract

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease primarily characterized by bilateral symmetrical polyarticular arthritis, which is often erosive. It is a common autoimmune disease (about1% of the world population), affects three times as many women as men, and usually appears in middle age (Poulsom & Charles , 2007). This disease is characterized by chronic synovial inflammation and synovial cell proliferation producing the pannus. Pannus development is related to mononuclear cell infiltration, neoangiogenesis, and abnormal proliferation of type-B synoviocytes or fibroblast-like synoviocytes (FLS) (Bartok & Firestein ,2010). (Dkk-1) is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the WNT signaling pathway. DKK1 appears to actively participate in joint damaging and joint remodeling in RA animal models, Recent studies confirmed its involvement in the remodeling process of the articular bone loss and repairing in human systemic rheumatic diseases such as RA. The authors proposed that DKK-1 is a master regulator of joint remodeling, shifting the balance from bone resorption, when its expression is increased, to new bone formation, when its expression is inhibited. This thesis was carried out to study the possible role of Dkk-1 in diagnosis of RA by measuring its serum level and relating it to disease activity and severity.