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2007 Fiscal Year Final Research Report Summary

The mechanism of low back pain and establish for new strategy of treatment

Research Project

Project/Area Number 18591626
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionUniversity of Yamanashi

Principal Investigator

HARO Hirotaka  University of Yamanashi, Department of Orthopaedic Surgery,Interdiatfinary, graduate school of Medicine and Engineering, Assistant Professor (10313264)

Co-Investigator(Kenkyū-buntansha) HAMADA Yoshiki  University of Yamanashi, Department of Orthopaedic Surgery Interdisciplinary graduate school of Medicine and Engineering, Professor (80096544)
TAKEDA Shu  Tokyo Medical and Dental University, Department of Orthopaedic Surgery, Visiting Associate Professor (30376727)
NAKAO Atuhito  University of Yamanashi, Department of Immunology, Interdisciplinary graduate school of Medicine and Engineering, Professor (80317445)
HARA Yasushi  Nippon Veterinary and Science University, Department of Surgery, Associate Professor (00228628)
ASOU Yoshinori  Tokyo Medical and Dental University, Department of Orthopaedic Surgery, Assistant Professor (50345279)
Project Period (FY) 2006 – 2007
KeywordsTEWAK / Degeneration of intervertebral disc / MMP-3
Research Abstract

The goal of this research was to examine the role of TWEAK in normal disc cells and to investigate its potential role in disc degeneration. We performed histological examinations of disc tissues and assessed the role of the novel cytokine TWEAK using murine organ disc culture. The expression of both TWEAK and its receptor, Fn14, in discs was confirmed by immunohistochemistry and quantitative real time PCR. TWEAK induced disc cells to generate MMP-3 in a dose- and time-dependent manner. This induction was strongly inhibited in the presence of a neutralizing antibody to TWEAK or a chimeric Fn14/Fc fusion protein. In disc tissues derived from TNF-a receptor 1- or TNF-a receptor 2-deficient mice, recombinant TWEAK modestly induced MMP-3. In contrast, in disc cultures lacking TWEAK, tissues from wild type mice or receptor-deficient mice failed to express MMP-3. Furthermore, aggrecan expression was potently abrogated in a time-dependent manner in the presence of recombinant TWEAK. This is the first report to confirm expression of TWEAK and its receptor Fn14 in murine intervertebral disc tissues. The data suggest that TWEAK plays a role in MMP-3 up-regulation and aggrecan down-regulation in disc tissues, resulting in proteoglycan degradation and promotion of disc degeneration.

  • Research Products

    (6 results)

All 2007

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (2 results)

  • [Journal Article] 椎間板変性と高齢者椎間板ヘルニアの病態2007

    • Author(s)
      波呂浩孝、濱田良機
    • Journal Title

      脊椎脊髄ジャーナル 20(5)

      Pages: 494-499

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Novel function of TWEAK in inducing intervertebral disc degeneration2007

    • Author(s)
      Masanori Wako, Hirotaka Haro
    • Journal Title

      Journal of Orthopaedic Research 25

      Pages: 1438-1446

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Disc degeneration and the pathological mechanism of aged intervertebral disc2007

    • Author(s)
      Hirotaka, Haro, Yoshiki, Hamada
    • Journal Title

      No.20(5)

      Pages: 494-499

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel function of TWEAK in inducing intervertebral disc degeneration2007

    • Author(s)
      Masanori, Wako, Hirotaka, Haro
    • Journal Title

      No.25

      Pages: 1438-1446

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Novel function of TWEAK in inducing intervertebral disc degeneration2007

    • Author(s)
      若生政憲、波呂浩孝
    • Organizer
      Journal of Orthopaedic Research
    • Place of Presentation
      浜松
    • Year and Date
      2007-10-27
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Novel function of TWEAK in inducing intervertebral disc degeneration2007

    • Author(s)
      Masanori, Wako, Hirotaka, Haro
    • Organizer
      the Japanese Orthopaedic Association
    • Place of Presentation
      Hamamatu Shizuoka Japan
    • Year and Date
      2007-10-27
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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