Wnt signaling in rheumatoid synoviocyte activation

Rheumatoid arthritis (RA) is a joint-specific disease with complex pathogenesis. It is characterized by synovial inflammation, cartilage loss, and joint destruction. The reasons why joint damage recurs when therapy is discontinued are not clearly understood. Several lines of evidence suggest that cartilage damage is promoted by the transformed and invasive fibroblast-like synoviocytes (FLS) of the rheumatoid joint. It has been demonstrated in several systems that aberrant wnt-mediated signaling causes blockade of cartilage differentiation and malformation of joints. In this review, we have discussed the importance of wnt–frizzled-mediated signaling in the autonomous activation of FLS in patients with RA. Anti-wnt/anti-frizzled antibodies, frizzled receptor antagonists, or small molecule inhibitors of wnt–frizzled signaling might be useful for therapeutic interventions in RA. Received: May 15, 2001/Accepted: September 28, 2001