Rheumatoid arthritis is an inflammatory disease that is also characterized by hypertrophy of the synovial lining. The reason for the accumulation of synovial cells in the rheumatoid joint remains unclear. It could be due to excessive proliferation of cells or, alternatively, to failure of cells to undergo normal senescence and death by apoptosis. In a recent study in Nature Medicine, Taniguchi et al1 report that rheumatoid synovial fibroblasts differ from osteoarthritis and normal synovial fibroblasts, as well as from skin and lung fibroblasts, in the regulation of a tumor suppressor gene. This gene, known as p16INK4a, is called a senescence gene because its expression is highest in senescent and terminally differentiated cells that are unable to proliferate. The investigators found that this gene is suppressed in all types of fibroblasts when they are grown in vitro. However, if the cells are manipulated by removing growth medium or by irradiating the cells, p16INK4a gene expression is upregulated in rheumatoid synovial fibroblasts but not the other types of fibroblasts. In conjunction with upregulation of the p16INK4a gene, rheumatoid fibroblasts became unresponsive to further attempts to stimulate growth. Furthermore, the investigators demonstrated that transfection of the joints of arthritic rats with this gene could ameliorate the signs and symptoms of arthritis, as well as reduce the damage to cartilage.
These interesting findings suggest that proliferation of rheumatoid synovial cells may have some unique intrinsic properties that are not shared by other types of fibroblasts. In addition, they suggest that induction of this gene in patients with rheumatoid arthritis may constitute a novel approach to the treatment of rheumatoid arthritis.
1Taniguchi K, Kohsaka H, Inoue N, et al. Nature Medicine 5:760-767, 1999.
