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- Title
Induction of the p16<sup>INK4a</sup> senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis.
- Authors
Taniguchi, Ken; Kohsaka, Hitoshi; Inoue, Naoki; Terada, Yoshio; Ito, Hiroshi; Hirokawa, Katsuiku; Miyasaka, Nobuyuki
- Abstract
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[sub 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[sub INK4a] gene efficiently inhibited the pathology in an animal model of rheumatoid arthritis. Thus, the induction of p16[sub INK4a] may provide a new approach to the effective treatment of rheumatoid arthritis.
- Publication
Nature Medicine, 1999, Vol 5, Issue 7, p760
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/10480