Basic FGF-induced activation of telomerase in rheumatoid synoviocytes.
To investigate the mechanism of persistent proliferation of rheumatoid arthritis (RA) synoviocytes in situ, we examined the activity of telomerase enzyme and the expression of telomerase related factors in cultured synoviocytes. Cultured synoviocytes obtained from patients with rheumatoid arthritis (n = 29), osteoarthritis (OA, n = 18), and traumatic joint disease (TJD, n = 4) were examined. Telomerase activity was detected by TRAP (telomeric repeat amplification protocol) assay, and 12 out of 29 samples of synoviocytes (41%) from RA patients showed a positive telomerase activity, whereas none of the samples from OA and TJD patients showed this activity. Results were confirmed by PCR-ELISA. The telomerase activity was enhanced by basic fibroblast growth factor (bFGF). The mRNA expression of telomerase related factors, such as hTERC, TRF2, and TEP-1, showed no difference between RA and OA synoviocytes. Our results suggest that telomerase is activated in rheumatoid synoviocytes, and that bFGF upregulates the activity of this enzyme in RA synoviocytes.
Tsumuki
H
H
Rheumatology, Immunology, and Genetics Program, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan.
Hasunuma
T
T
Kobata
T
T
Kato
T
T
Uchida
A
A
Nishioka
K
K
D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D016916:Joint Deformities, Acquired / Q000201:enzymology / Q000503:physiopathology; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D013583:Synovial Membrane / Q000201:enzymology / Q000503:physiopathology*; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C104342:TEP1 protein, human; D035341:Telomeric Repeat Binding Protein 2; D016222:Fibroblast Growth Factor 2; D019098:Telomerase