Nature Medicine
5, 760 - 767 (1999)
doi:10.1038/10480
Induction of the p16INK4a senescence gene as a new therapeutic
strategy for the treatment of rheumatoid arthritisKen Taniguchi1, Hitoshi Kohsaka1, Naoki Inoue1, Yoshio Terada2, Hiroshi Ito2, Katsuiku Hirokawa3
& Nobuyuki Miyasaka11
First Department of Internal Medicine, Tokyo Medical
and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. 2
Second Department of Internal Medicine, Tokyo Medical
and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
3
Department of Pathology and Immunology, School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima,
Bunkyo-ku, Tokyo, 113-8519, Japan
Correspondence should be addressed to Hitoshi Kohsaka kohsaka.med1@med.tmd.ac.jpSynovial 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.
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