Synovial tissue affected by rheumatoid arthritis is characterized by proliferation, which leads to irreversible cartilage and bone destruction. Current and experimental
treatments have been aimed mainly at correcting the underlying immune abnormalities, but these treatments often prove ineffective in preventing the invasive destruction.
We studied the expression of cyclin-dependent kinase inhibitors in rheumatoid
synovial cells as a means of suppressing synovial cell proliferation. Synovial
cells derived from hypertrophic synovial tissue readily expressed p16
INK4a when they were growth-inhibited. This was not seen in other
fibroblasts, including those derived from normal and osteoarthritis-affected
synovial tissues. In vivo adenoviral gene therapy with the p16
INK4a gene efficiently inhibited the pathology in an animal model
of rheumatoid arthritis. Thus, the induction of p16INK4a may
provide a new approach to the effective treatment of rheumatoid arthritis.
