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Elucidation of pathogenesis of low back pain related to degeneration of intervertebral disc and development of minimally invasive treatment system

Research Project

Project/Area Number 15H03033
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Medical systems
Research InstitutionKobe University

Principal Investigator

Nishida Kotaro  神戸大学, 医学研究科, 特命教授 (00379372)

Co-Investigator(Kenkyū-buntansha) 高田 徹  神戸大学, 医学研究科, 医学研究員 (00598526)
由留部 崇  神戸大学, 医学部附属病院, 特定助教 (10514648)
角谷 賢一朗  神戸大学, 医学研究科, 助教 (10533739)
前野 耕一郎  神戸大学, 医学研究科, 医学研究員 (70403269)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Keywords椎間板変性 / 腰痛 / 遺伝子治療 / 腰部脊柱管狭窄 / 動物モデル / 低侵襲治療 / 脊椎疾患 / 椎間板 / 固定術 / 低侵襲手術システム / 低侵襲脊椎手術 / 棘突起間スペーサー / 腰部脊柱管狭窄症 / 椎間板ヘルニア / オートファジー / 免疫特権 / mTOR経路 / Raptor / RNA干渉
Outline of Final Research Achievements

Three types of disc degeneration models, which are indispensable for intervertebral disc research, have been established. Using the model that causes gradual degeneration, especially during the compression period, the notochord-derived cells disappeared early and the non-notochord-derived cells (recommending chondroid cells) relatively increased. In experiments using a dynamic loading culture device, pressure loading revealed that the involvement of a typical mechanoreceptor, integrin, is involved in disc degeneration. We made a spacer that can be inserted from the small skin in the posterior of the spine, made improvements including peripheral equipment, and confirmed by conducting large animal experiments for efficacy.

Academic Significance and Societal Importance of the Research Achievements

腰痛性疾患は社会的に極めて重要であり、その多くは椎間板変性に由来している。しかしながらその詳細はわかっておらず、研究のための椎間板変性モデルの作成無くしては先に進めない。これらのモデルを用いて椎間板変性のKey factorを特定し、それをターゲットにした分子生物学的なアプローチにより変性椎間板の再生あるいは変性の進行抑制が可能であれば社会的意義は多大である。また、腰部脊柱管狭窄症は高齢社会におけるADL障害を呈する疾患として極めて重要であり、低侵襲手術方法の開発も極めて重要と考える。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (26 results)

All 2019 2018 2017 2016 2015

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (21 results) (of which Int'l Joint Research: 8 results,  Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Pharmacological inhibition of mTORC1 but not mTORC2 protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism through Akt and autophagy induction.2019

    • Author(s)
      Kakiuchi Y, Yurube T, Kakutani K, Takada T, Ito M, Takeoka Y, Kanda Y, Miyazaki S, Kuroda R, Nishida K.
    • Journal Title

      Osteoarthritis Cartilage

      Volume: Epubahead of print Issue: 6 Pages: 1-19

    • DOI

      10.1016/j.joca.2019.01.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] オートファジーと椎間板変性2018

    • Author(s)
      由留部 崇、伊藤雅明、角谷賢一郎、高田 徹、黒田良祐、西田康太郎
    • Journal Title

      別冊 BIO Clinica

      Volume: 7 Pages: 20-23

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Selective interference of mTORC1/RAPTOR protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism with Akt and autophagy induction.2017

    • Author(s)
      Ito M, Yurube T, Kakutani K, Maeno K, Takada T, Terashima Y, Kakiuchi Y, Takeoka Y, Miyazaki S, Kuroda R, Nishida K.
    • Journal Title

      Osteoarthritis Cartilage

      Volume: 25 Issue: 12 Pages: 2134-2146

    • DOI

      10.1016/j.joca.2017.08.019

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] オートファジーの抑制はヒト椎間板細胞においてアポトーシス・セネッセンスを誘導するが、細胞外基質代謝への影響は少ない2018

    • Author(s)
      伊藤 雅明+、由留部 崇*、角谷 賢一朗*、髙田 徹、垣内 裕司+、武岡 由樹+、神田 裕太郎+、黒田 良祐*、西田 康太郎*
    • Organizer
      日本脊椎脊髄病学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] テムシロリムスのヒト椎間板髄核細胞保護効果はオートファジー及びAktの活性化に由来する2018

    • Author(s)
      垣内 裕司+、由留部 崇*、角谷 賢一朗*、高田 徹、伊藤 雅明+、武岡 由樹+、神田 裕太郎+、黒田 良祐*、西田 康太郎*
    • Organizer
      日本脊椎脊髄病学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Autophagy plays protective roles against human disc cellular apoptosis, senescence, and extracellular matrix degradation2018

    • Author(s)
      Masaaki Ito+, Takashi Yurube*, Kenichiro Kakutani*, Toru Takada, Yuji Kakiuchi+, Yoshiki Takeoka+, Yutaro Kanda+, Ryosuke Kuroda*, Kotaro Nishida*
    • Organizer
      International Society for the Study of the Lumbar Spine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Temsirolimus is a candidate of the optimal mTOR inhibitor to protect human disc cells depending on Akt and autophagy induction2018

    • Author(s)
      Yuji Kakiuchi+, Takashi Yurube*, Yoshiki Takeoka+, Masaaki Ito+, Yutaro Kanda+, Kenichiro Kakutani*, Toru Takada, Ryosuke Kuroda*, Kotaro Nishida*
    • Organizer
      International Society for the Study of the Lumbar Spine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The fate of notochordal cell in intervertebral disc degeneration induced by dynamic compressive load through integrin alpha5/beta1 mechanotransduction2018

    • Author(s)
      Yutaro Kanda+, Kenichiro Kakutani*, Yusuke Morita, Takashi Yurube*, Masaaki Ito+, Yuji Kakiuchi+, Yoshiki Takeoka+, Takuto Kurakawa, Yoshiki Terashima, Toru Takada, Ryosuke Kuroda*, Kotaro Nishida*
    • Organizer
      International Society for the Study of the Lumbar Spine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 動的圧迫負荷が,integrina5B1を介して脊索由来細胞に与える影響2018

    • Author(s)
      神田 裕太郎+、角谷 賢一朗*、森田 有亮、由留部 崇*、垣内 裕司+、武岡 由樹+、蔵川 拓外、髙田 徹、土井田 稔、西田 康太郎*、黒田 良祐*
    • Organizer
      日本整形外科学会基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] オートファジーの抑制はヒト椎間板細胞においてアポトーシス・セネッセンスを誘導するが、細胞外基質代謝への影響は少ない2018

    • Author(s)
      伊藤雅明、由留部 崇、角谷賢一朗、前野耕一郎、高田徹、寺嶋良樹、垣内裕司、武岡由樹、黒田良祐、西田康太郎
    • Organizer
      第47回日本脊椎脊髄病学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 椎間板動的圧迫負荷が脊索由来髄核細胞に及ぼした影響2018

    • Author(s)
      神田祐太郎、角谷賢一朗、森田有亮、由留部 崇、伊藤雅明、垣内裕司、武岡由樹、蔵川拓外、寺島良樹、高田 徹、黒田良祐、西田康太郎
    • Organizer
      第47回日本脊椎脊髄病学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Autophagy plays protective roles against human disc cellular apoptosis, senescence, and extracellular matrix degradation2018

    • Author(s)
      M. Ito, T. Yurube, K. Kakutani, T. Takada, Y. Kakiuchi, Y. Takeoka, Y. Kanda, R. Kuroda, K. Nishida
    • Organizer
      45th The International Society for the Study of the Lumbar Spine
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] オートファジーの抑制はヒト椎間板細胞においてアポトーシス、セネッセンスを誘導し、細胞数を減少させる2017

    • Author(s)
      伊藤雅明、由留部 崇、角谷賢一朗、前野耕一郎、高田徹、寺嶋良樹、垣内裕司、武岡由樹、黒田良祐、西田康太郎
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脊椎椎間板変性へのオートファジーの関与とその脊索由来細胞における恒常性維持機構の可能性2017

    • Author(s)
      由留部 崇、伊藤雅明、垣内裕司、寺島良樹、武岡由樹、角谷賢一郎、前野耕一郎、高田 徹、黒田良祐、西田康太郎
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ATG5のノックダウンによるオートファジーの抑制はヒト椎間板細胞のアポトーシスとセネッセンスを誘導し、細胞数を減少させる2017

    • Author(s)
      伊藤雅明、由留部 崇、角谷賢一朗、前野耕一郎、高田 徹、寺嶋良樹、垣内裕司、武岡由樹、黒田良祐、西田康太郎
    • Organizer
      第46回日本脊椎脊髄病学会学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] 椎間板髄核におけるオートファジーの重要性とその脊索表現型保持への関与の可能性2017

    • Author(s)
      由留部 崇、伊藤雅明、垣内裕司、寺島良樹、武岡由樹、角谷賢一郎、前野耕一郎、高田徹、黒田良祐、西田康太郎
    • Organizer
      第46回日本脊椎脊髄病学会学術集会
    • Related Report
      2016 Annual Research Report
  • [Presentation] Involvement of autophagy in intervertebral disc degeneration and its possible contribution to the maintenance of notochordal cell homeostasis2017

    • Author(s)
      Takashi Yurube, Hiroaki Hirata, Masaaki Ito, Yoshiki Terashima, Yuji Kakiuchi, Yoshiki Takeoka, Shingo Miyazaki, Kenichiro Kakutani, Koichiro Maeno, Toru Takada, Ryosuke Kuroda, Kotaro Nishida
    • Organizer
      The 44th International Society for the Study of the Lumbar Spine(国際学会)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inhibition of autophagy through ATG5 knock down induces apoptosis and senescence in human intervertebral disc cells2017

    • Author(s)
      Masaaki Ito, Takashi Yurube, Kenichiro Kakutani, Koichiro Maeno, Toru Takada, Yoshiki Terashima, Yuji Kakiuchi, Yoshiki Takeoka, Ryosuke Kuroda, Kotaro Nishida
    • Organizer
      The 44th International Society for the Study of the Lumbar Spine(国際学会)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 腰部脊柱管狭窄症に対する最小侵襲手術を目指した棘突起間スペーサーの開発2016

    • Author(s)
      西田康太郎、前野耕一郎、角谷賢一朗、由留部 崇、高田 徹、伊藤雅明、寺嶋良樹、垣内裕司、武岡由樹
    • Organizer
      第24回 日本腰痛学会
    • Place of Presentation
      山梨
    • Year and Date
      2016-09-02
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Selective interference of mTOR signaling is protective against human disc cellular apoptosis, senescence, and extracellular matrix degradation with autophagy induction2016

    • Author(s)
      to M., Yurube T., Kakutani K., Maeno K., Takada T., Miyazaki S., Terashima Y., Kakiuchi Y., Kurosaka M., Nishida K.
    • Organizer
      The International Society for the Study of the Lumbar Spine
    • Place of Presentation
      Singapore
    • Year and Date
      2016-05-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intervertebral disc nucleus pulposus has intensive involvement of autophagy compared to other musculoskeletal tissues and its degeneration is linked with decreased autophagy2016

    • Author(s)
      Yurube T., Hirata H., Ito M., Kakiuchi Y., Kakutani K., Maeno K., Takada T., Miyazaki S., Terashima Y., Kurosaka M., Nishida K.
    • Organizer
      The International Society for the Study of the Lumbar Spine
    • Place of Presentation
      Singapore
    • Year and Date
      2016-05-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mTORシグナル経路への選択的な干渉はオートファジーとAktの活性化を誘導し、ヒト椎間板細胞における細胞死、老化と細胞外気質分解を抑制する2016

    • Author(s)
      伊藤雅明、由留部崇、角谷賢一朗、前野耕一郎、高田徹、宮崎真吾、寺島良樹、垣内裕司、黒坂昌弘、西田康太郎
    • Organizer
      第45回 日本脊椎脊髄病学会
    • Place of Presentation
      千葉
    • Year and Date
      2016-04-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 椎間板では他の筋骨格系組織よりもオートファジーの関与が大きく、その活性は変性とともに減少する:オートファジー制御による椎間板変性予防の可能性2016

    • Author(s)
      由留部崇、平田裕亮、伊藤雅明、垣内裕司、角谷賢一朗、前野耕一郎、高田徹、宮崎真吾、寺島良樹、黒坂昌弘、西田康太郎
    • Organizer
      第45回 日本脊椎脊髄病学会
    • Place of Presentation
      千葉
    • Year and Date
      2016-04-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] 神戸大式棘突起間スペーサーの開発2015

    • Author(s)
      西田康太郎、前野耕一郎、角谷賢一朗、由留部崇
    • Organizer
      第14回 関西MISt 研究会
    • Place of Presentation
      大阪
    • Year and Date
      2015-07-11
    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] 棘突起間インプラント2018

    • Inventor(s)
      西田康太郎
    • Industrial Property Rights Holder
      神戸大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] PCT出願2018

    • Inventor(s)
      西田康太郎 他
    • Industrial Property Rights Holder
      神戸大学法人
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2017 Annual Research Report
    • Overseas

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Published: 2015-04-16   Modified: 2020-03-30  

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