Abstract
Pathology of rheumatoid arthritis is characterized by lymphocyte and macrophage infiltration and subsequent proliferation of synovial fibroblasts. The proliferative synovial tissue is called pannus, which destroys cartilage and bones of the affected joints. Most of the previous studies to develop new therapeutic approaches addressed how the synovial lymphocytes and macrophages are activated. We attempted to reveal abnormality of cell cycle control of the synovial cells and found that cyclindependent kinase inhibitors p16INK4a and p21Cip1 are readily inducible in the rheumatoid synovial fibroblasts. These inhibitors negatively regulate cell cycle of the mature cells, and actually suppressed proliferation of the synovial fibroblasts when their genes were adenovirally transferred. In vivo gene delivery of these genes into the joints of animals affected with experimental RA models suppressed pathology of the arthritis. The results showed that induction of CDKI in the synovial tissues could be a new therapeutic approach to treatment of rheumatoid arthritis.
