Induction of the p16(INK4a) senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis

Synovial tissue affected by rheumatoid arthritis is characterized by prolif eration, which leads to irreversible cartilage and bone destruction. Curren t and experimental treatments have been aimed mainly at correcting the unde rlying immune abnormalities, but these treatments often prove ineffective i n preventing the invasive destruction. We studied the expression of cyclin- dependent kinase inhibitors in rheumatoid synovial cells as a means of supp ressing synovial cell proliferation. Synovial cells derived from hypertroph ic synovial tissue readily expressed p16(1NK4a) when they were growth-inhib ited. This was not seen in other fibroblasts, including those derived from normal and osteoarthritis-affected synovial tissues. In vivo adenoviral gen e therapy with the p16(1NK4a) gene efficiently inhibited the pathology in a n animal model of rheumatoid arthritis. Thus, the induction of p16(1NK4a) m ay provide a new approach to the effective treatment of rheumatoid arthriti s.