| Project/Area Number |
17591577
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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 | The University of Tokushima |
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Principal Investigator |
NAKANO Shunji The University of Tokushima, Tokushima University Hospital, Lecturer, 医学部・歯学部附属病院, 講師 (60294683)
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| Co-Investigator(Kenkyū-buntansha) |
NIKAWA Takeshi The University of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院ヘルスバイオサイエンス研究部, 助教授 (20263824)
YASUI Natsuo The University of Tokushima, Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (00157984)
KAWASAKI Yoshiteru The University of Tokushima, Institute of Health Biosciences, Department of Orthopedics, Assistant Lecturer, 大学院ヘルスバイオサイエンス研究部, 助手 (00403733)
江川 洋史 徳島大学, 医学部・歯学部附属病院, 助手 (20359912)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | mast cell tryptase / protease activated receptor / rheumatoid arthritis / osteoarthritis / synovial fibroblast-like cell / IL-8 / synovial fluid / synovium |
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| Research Abstract |
The purpose of this study is to clarify the pathophysiological significance of thrombin and mast cell tryptase in articular lesions of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).
We obtained the following results.
1. Thrombin and mast cell tryptase (MCT) activity in synovial fluid were significantly higher in RA than in osteoarthritis (OA) and healthy subjects. In synovial tissue, MCT activity was similar in RA and OA.
2. There was no significant difference in synovial PAR expression between RA and OA, except for expression of PAR-2 mRNA transcripts
3. Thrombin and MCT enhanced the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells.
4. Furthermore, PAR-2 activating peptide stimulated the release of IL-8 from synovial fibroblast-like cells, suggesting that mast cell tryptase in synovial fluid stimulates the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells via activation of PAR-2.
5. This study showed that an unglycosylated form of mast cell tryptase accumulated in higher concentration in synovial fluid from RA relative to OA, and that there was higher expression of synovial PAR-2 mRNA transcripts in RA compared with that in OA.
In summary, higher secretion of mast cell tryptase and thrombin into synovial fluids in RA relative to OA stimulates higher proliferation of the synovium and production of proinflammatory cytokine in SFCs in RA compared with OA.
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