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The Role of Midkine in the Pathogenesis of Rheumatoid Arthritis

Research Project

Project/Area Number 15590270
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionNagoya University

Principal Investigator

MURAMATSU Hisako  Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (50182134)

Co-Investigator(Kenkyū-buntansha) KADOMATSU Kenji  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (80204519)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsmidkine / rheumatoid arthritis / MK-deficient mouse / antibody-mediated arthritis / osteoclast / antisense oligo DNA / synovial membrane / 関節炎モデル / マクロファージ
Research Abstract

Midkine(MK) is heparin-binding growth factor which promotes growth, survival and migration of various cells. The essential role of MK in migration of inflammatory cells has been shown using mice deficient in the MK gene. Here, we investigated the role of MK in the pathogenesis of rheumatoid arthritis(RA). MK levels in the sera and synovial fluid were increased in most cases of patients with RA, indicating a strong correlation between MK expression and RA. MK was expressed in macrophage-like cells and fibroblast-like cells in synovial membranes from the patients. In antibody-mediated arthritis, mice deficient in the MK gene seldom developed the disease, while most of the wild-type mice did. Administration of MK to the deficient mice increased the frequency of antibody-induced arthritis. Migration of inflammatory leukocytes to the synovial membranes in the disease models was suppressed in the MK-deficient mice. Furthermore, MK was found to promote the differentiation of osteoclasts from macrophages. In conclusion, MK participates in each of the two distinct phases of RA development, namely, migration of inflammatory leukocytes and osteoclast differentiation, and is a key molecule in the pathogenesis of RA.

Report

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

    (18 results)

All 2004 2003 Other

All Journal Article (14 results) Publications (4 results)

  • [Journal Article] Midkine, a Heparin-Binding Growth Factor, Is Fundamentally Involved in the Pathogenesis of Rheumatoid Arthritis2004

    • Author(s)
      Maruyama, K.
    • Journal Title

      Arthritis Rheum. 50

      Pages: 1420-1429

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding cytokine, plays key roles in intraperitoneal adhesions.2004

    • Author(s)
      Inoh, K.
    • Journal Title

      Biochem.Biophys.Res.Commun. 317

      Pages: 108-113

    • 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] The role of midkine and pleiotrophin in liver regeneration.2004

    • Author(s)
      Ochiai, K.
    • Journal Title

      Liver Int. 24

      Pages: 484-491

    • 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] α4β1- and α6β1-Integrins are functional receptors for midkine, a heparin binding growth factor.2004

    • Author(s)
      Muramatsu, H.
    • Journal Title

      J.Cell Sci. 117

      Pages: 5405-5414

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding growth factor, is fundamentally involved in the pathogenesis of rheumatoid arthritis.2004

    • Author(s)
      Maruyama, K., et al.
    • Journal Title

      Arthritis Rheum. 50

      Pages: 1420-1429

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Midkine, a heparin-binding cytokine, plays key roles hi intraperitoneal adhesions.2004

    • Author(s)
      Inoh, K., et al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 317

      Pages: 108-113

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of midkine and pleiotrophin in liver regeneration.2004

    • Author(s)
      Ochiai, K., et al.
    • Journal Title

      Liver Int. 24

      Pages: 484-491

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] α4β1-andα6β1-Integrins are functional receptors for midkine, a heparin-binding growth factor.2004

    • Author(s)
      Muramatsu, H., et al.
    • Journal Title

      J.Cell Sci. 117

      Pages: 5405-5415

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Midkine, a Heparin Binding Growth Factor, Is Fundamentally Involved in the Pathogenesis of Rheumatoid Arthritis2004

    • Author(s)
      Maruyama, K.
    • Journal Title

      Arthritis Rheum. 50

      Pages: 1420-1429

    • Related Report
      2004 Annual Research Report
  • [Journal Article] α4β1- and α6β1-Integrins are functional receptors for midkine, a heparin-binding growth factor.2004

    • Author(s)
      Muramatsu, H.
    • Journal Title

      J.Cell Sci. 117

      Pages: 5405-5415

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Receptor-type protein tyrosine phosphatase ζ as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons.2003

    • Author(s)
      Sakaguchi, N.
    • Journal Title

      Neurosci.Res. 45

      Pages: 219-224

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Recognition of glycosaminoglycan by midkine2003

    • Author(s)
      Muramatsu, T.
    • Journal Title

      Methods Enzymol. 363

      Pages: 365-376

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Receptor-type protein tyrosine phosphatase ζ as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons.2003

    • Author(s)
      Sakaguchi, N., et al.
    • Journal Title

      Neurosci.Res. 45

      Pages: 219-224

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Recognition of glycosaminoglycans by midkine.2003

    • Author(s)
      Muramatsu, T., et al.
    • Journal Title

      Methods Enzymol. 363

      Pages: 365-376

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Sakaguchi, N.: "Receptor-type protein tyrosine phosphatase z as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons"Neurosci.Res.. 45. 219-224 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Maruyama, K.: "Midkine a heparin-binding growth factor, is fundermentally involved in pathologenesis of Rheumatoid Arthitis"Arthritis Rheum.. (印刷中).

    • Related Report
      2003 Annual Research Report
  • [Publications] Ino, K.: "Midkine, a heparin binding cytokine play key roles in intraperitoneal adhesions"Biochem.Biophys.Res.Commun.. (印刷中).

    • Related Report
      2003 Annual Research Report
  • [Publications] Muramatsu, T.: "Recognition of glycosaminoglycans by midkine"Methods Enzymol.. 363. 365-376 (2003)

    • Related Report
      2003 Annual Research Report

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

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