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Abstract

The onset ratios and pathological conditions of collagen-induced arthritis and adjuvant arthritis in model mice and rats, respectively, were successfully ameliorated by topically expressing the cyclin-dependent kinase inhibitors p16and p21in articular tissues using adenoviral vectors. In the synovial cells of CDKI-transduced mice, expression of inflammatory cytokines was inhibited. Described are the use of the p21protein for inhibiting abnormal proliferation of synovial tissues, inflammation in synovial tissues and/or expression of inflammatory cytokines in synovial tissues; the p21gene; compounds promoting the activity or expression of the p21protein; and pharmaceutical compositions containing these molecules. Also provided are method of screening for compounds participating in the abnormal proliferation of synovial tissues, inflammation in synovial tissues and/or the expression of inflammatory cytokines in synovial tissues targeting the p21protein. Rheumatoid arthritis and other disorders associated with inflammation of the synovial tissue can be prevented or treated by promoting expression or function of p21protein.