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Molecular biologic approach to elucidate intervertebral disc degeneration and establishment of new treatment

Research Project

Project/Area Number 20591741
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, 大学院・医学工学総合研究部, 教授 (10313264)

Co-Investigator(Kenkyū-buntansha) NAKAO Atsushito  山梨大学, 大学院・医学工学総合研究部, 教授 (80317445)
HAMADA Yoshiki  山梨大学, 大学院・医学工学総合研究部, 教授 (80096544)
Co-Investigator(Renkei-kenkyūsha) TEKADA Shu  東京医科歯科大学, 医歯学総合研究科, COE拠点形成特別研究員(特任准教授) (30376727)
HARA Yasushi  日本獣医生命科学大学, 獣医学部, 助教授 (00228628)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2008: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
KeywordsTWEAK / MMP-3 / MCP-1 / 椎間板変性 / TNF-α / VEGF / angiogenesis
Research Abstract

Life time occurrence of low back pain goes up to 60-80%, and the most common complaint at outpatient clinic in Japan is LBP. The major cause of LBP is disc degeneration, that is acted by various kinds of cytokines and enzymes. The purpose of the current study is to explain the cause of the disc degenerations, moreover to examine the possibility of new cytokine treatment. The following below are our new findings conducted by the current study in the inflammation of herniated disc. (1) TWEAK, that is the TNF-α family, must induce MMP-3 and MCP-1 through C-Jun or NF-κβ signal pathway respectively. (2) TSLP must induce MCP-1 through NF-κβ signal pathway, resulting in Mφ infiltration. (3) TNF-α must induce VEGF with TNF-α receptor I, resulting in neovascuralization. However this phenomenon is decreased by aging. (4) The induction of MMP-3 and MCP-1 induced by TNF-α and TWEAK. However this induction is decreased by aging. I would like to continue investigation of this precise mechanism, moreover to achieve the establishment of new cytokine treatment in the future.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (18 results)

All 2011 2010 2009 2008 2007 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results) Presentation (10 results) Remarks (2 results)

  • [Journal Article] TNF-alfa induced NF-kappaB signaling reversed age-related declines in VEGF induction and angiogenic activity in intervertebral disc tissues.2009

    • Author(s)
      Ohba T, Haro H, Ando T, Wako M, Suenaga F, Aso Y, Koyama K, Hamada Y, Nakao A.
    • Journal Title

      J Orthop Res 27

      Pages: 229-235

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] TNF-alfa induced NF-KappaB signaling reverses age-related declines in VEGF induction and angiogenic activity in intervertebral disc tissues.2009

    • Author(s)
      Tetsuro Ohba
    • Journal Title

      J Orthop Res 27

      Pages: 229-235

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of signal transduction in TWEAK-induced matrix degradation by MMP-3 upregulation in disc tissues.2008

    • Author(s)
      Wako M, Ohba T, Ando T, Arai Y, Koyama K, Hamada Y, Nakao A, Haro H.
    • Journal Title

      Spine 33

      Pages: 2489-2494

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A potential role of TSLP in the recruitment of macrophages to mouse intervertebral disc cells via MCP-1 induction.2008

    • Author(s)
      Ohba T, Haro H, Ando T, Koyama K, Hatsushika K, Suenaga F, Ohnuma Y, Katoh R, Ogawa H, Hamada Y, Nakao A.
    • Journal Title

      Arthritis Res 58

      Pages: 3510-3519

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanism of signal transduction in TWEAK-induced matrix degradation by MMP-3 upregulationin disc tissues.2008

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

      Spine 33

      Pages: 2489-2494

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A potential role of TSLP in the recruitment of macrophages to mouse interveretebral disc cells via MCP-1 induetion.2008

    • Author(s)
      Tetsuro Ohba, Hirotaka Haro
    • Journal Title

      Arthritis & Rheumatism 58

      Pages: 3510-3519

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Age-related sequences of MCP-1 and MMP-3 expression in degeneration of mouse intervertebral disc.2011

    • Author(s)
      藤田康稚、安藤隆、大場哲郎、波呂浩孝
    • Organizer
      Annual meeting of Orthopaedic Research Society
    • Place of Presentation
      Long Beach, CA, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] Age-related sequences of MCP-1 and MMP-3 expression in degeneration of mouse intervertebral disc.2011

    • Author(s)
      藤田康稚
    • Organizer
      Orthopaedic Research Society
    • Place of Presentation
      USA(Long Beach, CA)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 炎症による椎間板性腰痛における加齢の影響2010

    • Author(s)
      藤田康稚、安藤隆、大場哲郎、波呂浩孝
    • Organizer
      第18回日本腰痛学会
    • Place of Presentation
      札幌
    • Year and Date
      2010-10-30
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] ヘルニア塊の退縮に対する加齢の影響について2010

    • Author(s)
      藤田康稚、大場哲郎、安藤隆、若生政憲、中尾篤人、波呂浩孝
    • Organizer
      第25回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-10-15
    • Related Report
      2010 Final Research Report
  • [Presentation] 老化に伴う椎間板変性の影響について2010

    • Author(s)
      藤田康稚
    • Organizer
      第25回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-10-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 椎間板細胞における炎症性反応の加齢による変化2010

    • Author(s)
      藤田康稚、安藤隆、大場哲郎、若生政憲、加藤良平、中尾篤人、波呂浩孝
    • Organizer
      第29回日本運動器移植・再生医学研究会
    • Place of Presentation
      京都
    • Year and Date
      2010-09-25
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] TSLPは、腰椎椎間板ヘルニアの自然退縮機序において、ヘルニア塊へのマクロファージの浸潤に作用している2009

    • Author(s)
      大場哲郎、若生政憲、小山賢介、藤田康稚、波呂浩孝
    • Organizer
      第24回日本整形外科学会基礎学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2009-11-06
    • Related Report
      2010 Final Research Report
  • [Presentation] 椎間板の血管新生に対するTNFαの作用、及び加齢の影響について。2009

    • Author(s)
      大場哲郎
    • Organizer
      日本整形外科学会学術総会基礎学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-11-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] 椎間板由来のサイトカイン産生におけるTNF-αのシグナル伝達経路の解析2008

    • Author(s)
      大場哲郎, 波呂浩孝
    • Organizer
      日本整形外科学会
    • Place of Presentation
      京都
    • Year and Date
      2008-10-23
    • Related Report
      2008 Annual Research Report
  • [Presentation] 椎間板由来のサイトカイン産生におけるTNF-αのシグナル伝達経路の解析2007

    • Author(s)
      大場哲郎、波呂浩孝、安藤隆、若生政憲、中尾篤人、浜田良機
    • Organizer
      第22回日本整形外科学会基礎学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2007-10-26
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • URL

      http://www.med.yamanashi.ac.jp/clinical/orthop/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.med.yamanashi.ac.jp/clinical/orthop/

    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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