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Analysis of functional disturbance of chondroctyes in oseoarthritis and establishment of new therapeutic strategies for the disease.

Research Project

Project/Area Number 15390467
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionClinical Research Center, National Hospital Organization Sagamihara Hospital

Principal Investigator

FUKUI Naoshi  National Hospital Organization Sagamihara Hospital, Clinical Research Center, Director of division, 病態総合研究部, 研究部長 (10251258)

Co-Investigator(Kenkyū-buntansha) TANAKA Sakae  The University of Tokyo, Department of Orthopaedic Surgery, Instructor, 医学部 整形外科・脊椎外科, 講師 (50282661)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥7,600,000 (Direct Cost: ¥7,600,000)
KeywordsOsteoarthritis / Laser Capture Microdissection / mRNA / real time PCR / Cartilage matrix / Chondrocyte / レーザー・マイクロダイセクション / 定量的PCR / lysyl oxidase / 細胞外基質 / II型コラーゲン / IX型コラーゲン / XI型コラーゲン / cDNAマイクロアレイ / 定量的RT-PCR / レーザーマイクロダイセクション / II形コラーゲン / アグリカン
Research Abstract

In this research project, we employed a technique of laser microdissection on osteoarthritic (OA) and normal cartilage and performed a detailed analysis on the functional alteration of chondrocyte with the disease. The findings obtained in this project are summarized below.
1.In OA cartilage, chondrocytes undergo a certain phenotypic change at the surface of degenerated areas, and the profile of matrix gene expression is altered. In those areas, the expression of cartilage matrix genes such as COL2A1 and aggrecan is suppressed, and instead, the expression of pathologically induced genes, such as COL3A1 and fibronectin, is enhanced. The change or the shift in the pattern of matrix gene expression might promote matrix loss in those areas by replacing the matrix with that of a poorer quality. Assuming this to be true, it might be possible that the progression of OA could be slowed down through the normalization of cellular functions at the surface of degenerated cartilage.
2.To date, no clear explanation has been give to the contradiction in the pathology of OA that the cartilage matrix is gradually lost in spite of enhanced matrix synthesis. The result of this project revealed, for the first time, that the synthetic activity by chondrocytes could be significantly impaired thorough the loss of balance in the expression of collagen genes. Even in macroscopically intact areas in OA cartilage, the expression of type IX and type XI collagen genes was relatively reduced compared with that of type II collagen. Based on the findings of human hereditary diseases and gene-manipulated mice, the reduction of these minor collagens could lead to the deterioration of cartilage matrix quality. Thus, from current results, the loss of cartilage matrix in OA could be enhanced through the disturbed matrix synthesis in OA chondrodytes.
Thus, the result of this project has revealed novel, important mechanisms in the pathology of OA.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005

All Journal Article (11 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Endoscopic anterior reconstruction using a computer-assisted fluoroscopic navigation system.2006

    • Author(s)
      Hiraoka H, Fukui N, et al.
    • Journal Title

      J Orthop Sci 11

      Pages: 159-166

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Effect of GDF-5 on ligament healing.2006

    • Author(s)
      Tahiro T, Fukui, N, et al.
    • Journal Title

      J Orthop Res 24

      Pages: 71-79

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endoscopic anterior cruciate ligament reconstruction using a computer-assisted fluoroscopic navigation system.2006

    • Author(s)
      Hiraoka H, Fukui N, et al.
    • Journal Title

      J Orthop Sci 11

      Pages: 159-166

    • NAID

      10017420584

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of GDF-5 on ligament healing2006

    • Author(s)
      Tahiro T, Fukui N, et al.
    • Journal Title

      J Orthop Res 24

      Pages: 71-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of GDF-5 on ligament healing.2006

    • Author(s)
      Tahiro T, Fukui, N, et al.
    • Journal Title

      J Orhtop Res 24

      Pages: 71-79

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid arthritis patients after simulation with monocytes.2005

    • Author(s)
      Tanaka K, Fukui N, et al.
    • Journal Title

      Mod Rheumatol 15

      Pages: 415-422

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of analternatively spliced variant of Ca2+ -promoted Ras inactivator as a possible regulator of RANKL shedding.2005

    • Author(s)
      Hikita A, Tanaka S, et al.
    • Journal Title

      J Biol Chem 280

      Pages: 41700-41706

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid arthritis patients after stimulation with monocytes.2005

    • Author(s)
      Tanaka K, Fukui N, et al.
    • Journal Title

      Modern Rheumatol 15

      Pages: 415-422

    • NAID

      10016914626

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Identification of alternatively spliced variant of Ca^<2+>-promoted Ras inactivator as possible regulator of RANKL shedding.2005

    • Author(s)
      Hikita A, Tanaka S, et al.
    • Journal Title

      J Biol Chem 280

      Pages: 41700-41706

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Production of interleukin-6 and interleukin-8 by nurse-like cells from rheumatoid arthritis patients after stimulation with monocytes.2005

    • Author(s)
      Tanaka K, Fukui N, et al.
    • Journal Title

      Mod Rheumatol 15

      Pages: 415-422

    • NAID

      10016914626

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Identification of an alternatively spliced variant of Ca^<2+>-promoted Ras inactivator as a possible regulator of RANKL shedding.2005

    • Author(s)
      Hikita A, Tanaka S, et al.
    • Journal Title

      J Biol Chem 280

      Pages: 41700-41706

    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] ヒト軟骨細胞形質維持因子2006

    • Inventor(s)
      福井尚志, 谷上 信
    • Industrial Property Rights Holder
      独立行政法人国立病院機構, 大塚製薬株式会社
    • Filing Date
      2006-05-22
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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

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