| Project/Area Number |
11470306
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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, Faculty of Medicine, Associate, 医学部, 助教授 (00219461)
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| Co-Investigator(Kenkyū-buntansha) |
YONEHARA Shin Kyoto Univ, Institute for Virus Research, Professor, ウイルス研究所, 教授 (00124503)
KIMURA Tomoatsu Toyama Medical and Pharmaceutical Univ, Faculty of Medicine, Professor, 医学部, 教授 (80167379)
YUDOH Kazuo St. Mariannna Univ, Institute of Medical Science, Assosistant Professor, 医学部, 助手 (60272928)
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| Project Period (FY) |
1999 – 2002
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| Keywords | Apoptosis / SCID-HuRAg mouse / Synovium / Cartilage / Rheumatoid Arthritis / Monocronal Antibody / Humanized Antibody / Matrix Metalloproteinase |
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| Research Abstract |
We developed a novel animal model of rheumatoid arthritis. This mouse model (SCID-HuRAg) is prepared by the fresh rheumatoid synovial tissue including joint cartilage is grafted subcutaneously into the backs of SCID mice. Histologic characteristics of the implanted tissues in SCID-HuRAg mice were very similar to those of human RA even 2 months after implantation. The SCID-HuRAg mouse is a useful model for evaluating the effectiveness of antirheumatic drugs. Therefore, 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 intraperitoneally. 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. CONCLUSION : 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.
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