Pathogenesis of RA:: more than just immune cells

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that primarily affects the joints and results in their progressive destruction. Research during past years has shown that in addition to inflammatory cells and their mediators, resident fibroblasts of the synovial membrane play an important role in the pathogenesis of the disease. These cells exhibit features of stable cellular activation that is maintained in the absence of continuous inflammatory stimuli. In contrast to normal synovial fibroblasts or fibroblasts from patients with osteoarthritis, RA synovial fibroblasts show an upregulation of proto-oncogenes and transcription factors, which in a self-perpetuating manner mediate the expression of adhesion molecules and matrix degrading enzymes, and result in alterations in apoptosis. As a consequence, these activated fibroblasts attach to cartilage and bone and progressively destroy articular structures. A better understanding of the molecular mechanisms that lead to the stable activation of synovial fibroblasts in RA is, therefore, of utmost importance for elucidating the pathogenesis of RA as well as for the development of novel therapeutic strategies aimed at inhibiting joint destruction.