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Clarification of the pathophysiological significance of mast cell tryptase and protease activated receptor-2 (PAR-2) in articular destruction

Research Project

Project/Area Number 15591581
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokushima

Principal Investigator

NAKANO Shunji  The University of Tokushima, University Medical and Dental Hospital, Lecturer, 医学部・歯学部附属病院, 講師 (60294683)

Co-Investigator(Kenkyū-buntansha) NIKAWA Takeshi  The University of Tokushima, Graduate School 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)
ENDO Kenji  The University of Tokushima, University Medical and Dental Hospital, Lecturer, 医学部・歯学部附属病院, 助手 (60325272)
EGAWA Hiroshi  The University of Tokushima, University Medical and Dental Hospital, Lecturer, 医学部・歯学部附属病院, 助手 (20359912)
YASUI Natsuo  The University of Tokushima, Graduate School 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)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsmast cell tryptase / protease activated receptor / rheumatoid arthritis / osteoarthritis / synovial fibroblast-like cell / IL-8 / synovial fluid / synovium / tryptase / thrombin / cathepsin B / protease-activated receptor / rheumatoid arthritis
Research Abstract

The purpose of this study is to clarify the pathophysiological significance of mast cell tryptase and protease activated receptor-2 (PAR-2) in articular lesions of patients with rheumatoid arthritis (RA).
We obtained the following results.
1.Trypsin-like activity in synovial fluid was significantly higher in RA than in osteoarthritis (OA) and healthy subjects, while in synovial tissue it was similar in RA and OA.
2.The expression of PAR-2 mRNA in synovial tissue was higher in RA than in OA.
3.The biochemical characteristics of trypsin-like enzyme purified from synovial tissue were similar to those of human mast cell tryptase.
4.Human mast cell tryptase enhanced the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells.
5.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.
In summary, trypsin-like activity in synovial fluid was significantly higher in RA than in OA and healthy subjects. Mast cell tryptase and activation of its receptor (PAR-2) enhanced the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells. Thus, in rheumatoid lesions, mast cell tryptase is involved in amplifying arthritis via PAR-2.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004 2003 Other

All Journal Article (18 results) Publications (2 results)

  • [Journal Article] Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population2005

    • Author(s)
      Hamada D. et al.
    • Journal Title

      Arthritis & Rheumatism (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclooxygenase-2 inhibitor delays early fracture healing in rats.2005

    • Author(s)
      Endo K.et al.
    • Journal Title

      Acta Orthopaedica Scandinavica (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population2005

    • Author(s)
      Hamada D. et al.
    • Journal Title

      Arthritis & Rheumatism (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Total hip arthroplasty in osteopetrosis using computer-assisted fluoroscopic navigation -A case report-2005

    • Author(s)
      Egawa H. et al.
    • Journal Title

      Journal of Arthroplasty (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Cyclooxygenase-2 inhibitor delays early fracture Healing in rats.2005

    • Author(s)
      Endo K.et al.
    • Journal Title

      Acta Orthopaedica Scandinavica. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population2005

    • Author(s)
      Hamada Daisuke et al.
    • Journal Title

      Arthritis & Rheumatism (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cyclooxygenase-2 inhibitor delays early fracture healing in rats.2005

    • Author(s)
      Endo Kenji et al.
    • Journal Title

      Acta Orthopaedica Scandinavica (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Relationship between cathepsin B and thorombin in rheumatoid arthritis2004

    • Author(s)
      Mishiro T. et al.
    • Journal Title

      Journal of Rheumatology 31・7

      Pages: 1265-1273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Influence of age on scapulo-thoracic orientation.2004

    • Author(s)
      Endo K.et al.
    • Journal Title

      Clinical Biomechanics. 19

      Pages: 1009-1013

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Skeletal muscle gene expression in space-flown rats2004

    • Author(s)
      Nikawa Takeshi. et al.
    • Journal Title

      FASEBJ 18

      Pages: 522-524

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of Autoimmune Arthritis With Aging Via Bystander T Cell Activation in the Mouse Model of Sjogren's Syndrome2004

    • Author(s)
      Kobayashi M
    • Journal Title

      Arthritis Rheum 50(12)

      Pages: 3974-3984

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Relationship between cathepsin B and thorombin in rheumatoid arthritis2004

    • Author(s)
      Mishiro T. et al.
    • Journal Title

      Journal of Rheumatology 71.3

      Pages: 1265-1273

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Skeletal muscle gene expression in space-flown rats.2004

    • Author(s)
      Nikawa T. et al.
    • Journal Title

      FASEB J. 18(3)

      Pages: 522-524

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Development of Autoimmune Arthritis With Aging Via Bystander T Cell Activation in the Mouse Model of Sjogren's Syndrome2004

    • Author(s)
      Kobayashi M. et al.
    • Journal Title

      Arthritis & Rheumatism 50(12)

      Pages: 3974-3984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Relationship between cathepsin B and thorombin in rheumatoid arthritis2004

    • Author(s)
      Mishiro Takuya et al.
    • Journal Title

      Journal of Rheumatology 31・7

      Pages: 1265-1273

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Skeletal muscle gene expression in space-flown rats2004

    • Author(s)
      Nikawa Takeshi.et al.
    • Journal Title

      FASEBJ 18

      Pages: 522-524

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Intracapsular hip fractures in patients with rheumatoid arthritis2003

    • Author(s)
      Hasan MY. et al.
    • Journal Title

      International Orthopaedics 27

      Pages: 294-297

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Total hip arthroplasty in osteopetrosis using computer-assisted fluoroscopic navigation - A case report-

    • Author(s)
      Egawa H. et al.
    • Journal Title

      Journal of Arthroplasty (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Mishiro T.: "Relationship between Cathepsin B and Thrombin in Rheumatoid Arthritis"Journal of Rheumatology. (In press). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hasan MY.: "Intracapsular hip fractures in patients with rheumatoid arthritis"International Orthopaedics. 27. 294-297 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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