K. Taniguchi et al., Induction of the p16(INK4a) senescence gene as a new therapeutic strategy for the treatment of rheumatoid arthritis, NAT MED, 5(7), 1999, pp. 760-767
Citations number
45
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
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.