1998 Fiscal Year Final Research Report Summary
Role of Apoptosis in Patients with Rheumatoid Arthritis
| Project/Area Number |
08671646
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Toyama Medical and Pharmaceutical University |
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Principal Investigator |
MATSUNO Hiroaki Toyama Medical and Pharmaceutical Univ.Orthopaedic Surgery Assistant Pro, 附属病院, 講師 (00219461)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Rheumatoid Arthritis / SCID-Hu RAg mouse / Apoptosis / Collagen Induce Arthritis / Interleikin-6 / Treatment / Joint destruction / Cytikine |
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| Research Abstract |
To investigate the time at which apoptotic cefls appear during the course of the synovitis in rheumatoid arthritis (RA4) patients, we conducted a time course observation change of apoptotic cells in collagen- induced arthritis mice as a RA model. As a result, no apoptotic cells were detected before the onset of synovit is the number of such cells increased parallel to the progress of arthritis in its initial stages, and the number of cells decreased in the proliferative stage of arthritis. These results suggested that apoptotic cells appeared to maintain the homeostasis when there was synovium proliferation which is undesirable for the morphological maintenance of a joint, If the induction of apoptosis is possible in RA synovitis, this procedure might lead to a cure for RA.Based on this hypothesis, the apoptosis ther apeutic experiments using anti- Fas mAb and Fas- ligand was investigated in SOlD- HuRAg mice implanted with human RA synovial tissues. As a result, the synovitis implanted in mice was reduced markedly, suggesting that apoptosis induction ther apr may be a novel treatment strategy for PA.Moreover, in order to examine the effect of anti- reshaping human IL- 6 receptor monoclonal antibody (rhIL-6RmAb) on patients with rheumatoid arthritis (RA), a treatment study was conducted using SClD-HuRAg mice. As a result, a significant decrease in the number of inflammatory cells, MMPs positive cells and the TRAP positive cells was observed in the anti - rhIL - 6RmAb treatment group as compared with the other control groups. The SCID- HuRAg mice were considered to be a useful model for the evaluation of the effectiveness of the anti- rheumatic drugs. ln addition, the possibility that the anti-rhlL-6RmAb treatment has an anti-inflammatory effect on RA synovitis and an inhibitory effect on osteoclast was suggested.
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