| Project/Area Number |
15591598
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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 | Iwate Medical University |
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Principal Investigator |
UZUKI Miwa (2005) Iwate Medical University, School of Medicine, Lecturer, 医学部, 教授 (50305992)
吉田 昌明 (2003-2004) 岩手医科大学, 医学部, 講師 (80210722)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAI Takashi Iwate Medical University, School of Medicine, Professor, 医学部, 教授 (00125577)
KANNO Hiroyuki Iwate Medical University, School of Medicine, Assistant. Professor, 医学部, 助教授 (40252663)
TAJIMA Katsumi Iwate Medical University, School of Medicine, Lecturer, 医学部, 講師 (80236520)
宇月 美和 岩手医科大学, 医学部, 講師 (50305992)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2005: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | rheumatoid arthritis / bone resorption / proteinase / osteoclast / osteoblast / Tリンパ球 / in situ hybridization / matrix metalloproteinase / TNF-α / マトリックスメタロプロテアーゼ / 破骨細胞分化誘導因子 / RANK |
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| Research Abstract |
Objective. In our study, matrix metalloproteinases (MMPs) were seen at the bone resorption area of the patients with rheumatoid arthritis. There are numerous osteoclasts in this area especially in RA joints. To examine the suppressive effect of anti-human Fas monoclonal antibody (mAb) on osteoclastogenesis in rheumatoid arthritis (RA) both in vitro and in vivo. Methods. For in vitro analysis, activated CD4(+) T cells derived from peripheral blood mononuclear cells were left untreated or were treated with humanized anti-human Fas mAb and cocultured with human monocytes. On day 12, the number of tartrateresistant acid phosphatase (TRAP)-positive multinucleated cells was counted. For in vivo analysis, tissue derived from human RA pannus was implanted with a slice of dentin subcutaneously in the backs of SCID mice (SCID-HuRAg-pit model). Anti-human Fas mAb was administered intravenously once a week for 3 weeks. The implanted tissue and dentin slice were removed, and the pits formed on the dentin slice were analyzed. Results. In vitro, coculture of activated CD4 (+) T cells and peripheral monocytes induced osteoclastogenesis. The number of TRAP-positive multinucleated cells was reduced when activated CD4(+) T cells were treated with anti-human Fas mAb. We established a new animal model for monitoring osteoclastogenesis, SCID-HuRAg-pit. We found that with anti-human Fas mAb treatment, the number of pits formed on the implanted dentin slices was significantly reduced and the number of lymphocytes in the implanted RA synovial tissue was dramatically reduced in this model. Conclusion. This is the first study to demonstrate the suppressive effect of anti-human Fas mAb on osteoclastogenesis in RA synovial tissues through the induction of T cell apoptosis. Induction of apoptosis of infiltrated lymphocytes could be a useful therapeutic strategy for RA, in terms of suppressing both inflammation and bone destruction.
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