The Role of the Synovial Fibroblast in Rheumatoid Arthritis: Cartilage Destruction and the Regulation of Matrix Metalloproteinases

Rheumatoid arthritis (RA) is a complex multisystem disease, the hallmark of which is pannus, the abnormal proliferative synovial tissue that serves as both propagator of the immune response and as the engine of tissue damage. Conceptually, pannus may be divided into two compartments (Fig. 1). The first, comprised by T cells, B cells, macrophages, and dendritic cells, is an immune compartment that exists in what was formerly the subintimal layer of normal synovium. These immune cells partake in antigen presentation, immunoglobulin production (including rheumatoid factor and anti-cyclic citrullinated protein [CCP] antibodies) and cytokine generation; the T cell is thought by many investigators to be the driving force coordinating these various activities.