Telomerase activation in lymphocytes may provide insights into the progression of synovitis and synovial proliferation in RA. Moreover, the enzyme may be implicated in the proliferation of synoviocytes in PVS.
Objective. To investigate whether Fas-mediated apoptosis has potential as a new therapeutic strategy in rheumatoid arthritis (RA) by use of a novel model of' RA in which human RA tissue is grafted into SCID mice. Methods. Fresh rheumatoid synovial tissue including joint cartilage was grafted subcutaneously into the backs of SCID mice. Six weeks after engraftment, anti-Fas monoclonal antibody was injected intraperito-neally. Time-related apoptotic changes caused by anti-Fas monoclonal antibody in grafted synovium were evaluated by nick end-labeling histochemistry. Results. Thirty-six hours after the injection, diffuse apoptotic changes were observed in the grafted synovia. Four weeks after the injection, rheumatoid synovial tissue diminished. ConcZusion. This is the first report concerning the present effectiveness of anti-Fas monoclonal antibody in diminishing rheumatoid synovium in vivo, and suggests the possibility of a new strategy for treating rheumatoid arthritis by inducing Fas-mediated apoptosis. Rheumatoid arthritis (RA) is a chronic inflam-matory disorder characterked by hyperplasia of the
Objective.To examine the effect of anti-reshaping human interleukin-6 receptor monoclonal antibody (anti-rsHuIL-6R mAb) on patients with rheumatoid arthritis (RA), using SCID mice in which human RA synovial tissue has been grafted (SCID-HuRAg).Methods. Tissue from human RA pannus was implanted subcutaneously in the backs of 69 SCID mice.Differences from human RA were examined pathologically. Anti-rsHuILdR mAb (100 pg) was administered intraperitoneally to mice once a week for 4 weeks. The implanted tissue was removed from the SCID-HuRAg mice on the fifth week after the initial treatment and examined pathologically. A group of SCID-HuRAg mice treated with control mAb, an auranofin-treated group, and an untreated group were used as controls. A total of 32 mice (8 in each group) were studied.Results. Histologic characteristics of the implanted tissues in SCID-HuRAg mice were very similar to those of human RA even 2 months after implantation. In addition, the presence of CD4-, CD8-, CD20-, IL-6-, tumor necrosis factor a-, tartrate-resistant acid phosphatase (TRAP)-, matrix metalloproteinase 1 (MMP-1)-, and MMP-9-positive cells was confirmed by
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