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Integrated research on intervertebral disc degeneration control targeting apoptotic response mechanism

Research Project

Project/Area Number 17K16669
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionHokkaido University

Principal Investigator

Yamada Katsuhisa  北海道大学, 医学研究院, 特任助教 (20771893)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords椎間板変性制御 / アポトーシス / Caspase3 / ノックアウトマウス / 医学 / 脊椎脊髄病学 / 椎間板変性
Outline of Final Research Achievements

We analyzed caspase-3’s role in two different types of intervertebral disc (IVD) degeneration using caspase-3 knockout (Casp-3 KO) mice.
Apoptosis was suppressed in the IVD cells of Casp-3 KO mice, but cellular senescence was enhanced. Casp-3 KO delayed IVD degeneration in the injury-induced model but accelerated it in the age-induced model. Our results suggest that this is due to different pathological mechanisms of these two types of IVD degeneration.
This would explain why the Casp-3 KO was effective against injury-induced, but not age-related, IVD degeneration. Our results suggest that short-term caspase-3 inhibition could be used to treat injury-induced IVD degeneration.

Academic Significance and Societal Importance of the Research Achievements

アポトーシス誘導遺伝子caspase3を抑制することで、外傷性椎間板変性の進行が遅延した一方、加齢性自然発症椎間板変性は増悪し、これらは異なる病態であることが本研究で明らかとなった。また、通常細胞死に至るべくある細胞のアポトーシスを人為的に抑制することにより細胞の腫瘍化等を引き起こすことが危惧されたが、caspase 3ノックアウトマウスの椎間板組織に腫瘍化細胞の出現は認めなかった。
本研究結果より、外傷性椎間板変性に対してcaspase 3 遺伝子の発現を一過性に抑制することは、椎間板組織変性制御として有用な治療手段となりうることが示唆された。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (17 results)

All 2020 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (13 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Mechanical Analysis of Notch-Free Pre-Bent Rods for Spinal Deformity Surgery2020

    • Author(s)
      Yamada Katsuhisa、Sudo Hideki、Iwasaki Norimasa、Chiba Akihiko
    • Journal Title

      SPINE

      Volume: 45 Issue: 6 Pages: E312-E318

    • DOI

      10.1097/brs.0000000000003269

    • NAID

      130008106292

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caspase-3 knockout inhibits intervertebral disc degeneration related to injury but accelerates degeneration related to aging2019

    • Author(s)
      Ohnishi T, Yamada K, Iwasaki K, Tsujimoto T, Higashi H, Kimura T, Iwasaki N, Sudo H
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 19324-19324

    • DOI

      10.1038/s41598-019-55709-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rapidly progressive cervical myelopathy had a high risk of developing deep venous thrombosis: a prospective observational study in 289 cases with degenerative cervical spine disease2018

    • Author(s)
      Yamada Katsuhisa、Suda Kota、Matsumoto Harmon Satoko、Komatsu Miki、Ushiku Chikara、Takahata Masahiko、Minami Akio、Iwasaki Norimasa
    • Journal Title

      Spinal Cord

      Volume: 57 Issue: 1 Pages: 58-64

    • DOI

      10.1038/s41393-018-0213-9

    • NAID

      120006626575

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Postoperative translation of the upper instrumented vertebra in thoracic adolescent idiopathic scoliosis2018

    • Author(s)
      Yamada Katsuhisa、Sudo Hideki、Kaneda Kiyoshi、Shono Yasuhiro、Abe Yuichiro、Iwasaki Norimasa
    • Journal Title

      Journal of Neurosurgery: Pediatrics

      Volume: 22 Issue: 6 Pages: 694-700

    • DOI

      10.3171/2018.6.peds18256

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Clinical Patterns, Epidemiology, and Risk Factors of Multidrug-Resistant Pyogenic Spondylitis in Thoraco-Lumbar Spine.2019

    • Author(s)
      Katsuhisa Yamada, Masahiko Takahata, Ken Nagahama, Akira Iwata, Tsutomu Endo, Takahi Onishi, Hideki Sudo, Manabu Ito, Norimasa Iwasaki
    • Organizer
      American Academy of Orthopaedic Surgeons 2019 Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 頚椎化膿性脊椎炎の臨床的特徴と機能予後 -後弯変形とQOLとの関連-2019

    • Author(s)
      山田 勝久,高畑 雅彦,楫野 知道,袖山 洋平,岩田 玲,小甲 晃史,遠藤 努,大西 貴士,須藤 英毅,石黒 信久,岩崎 倫政
    • Organizer
      第92回日本整形外科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膿胸・縦隔膿瘍を併発した胸椎化膿性脊椎炎に対する治療 -難治例では椎間板・胸腔ドレナージが必要-2019

    • Author(s)
      山田勝久 高畑雅彦 青木佑介 岩田玲 遠藤努 大西貴士 須藤英毅 石黒信久 岩崎倫政
    • Organizer
      第92回日本整形外科学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Epidemiology and Risk Factors of Multidrug-Resistant Pyogenic Spondylitis in Thoraco-Lumbar Spine.2019

    • Author(s)
      Katsuhisa Yamada, Masahiko Takahata, Ken Nagahama, Akira Iwata, Tsutomu Endo, Takahi Onishi, Hideki Sudo, Manabu Ito, Norimasa Iwasaki
    • Organizer
      46th annual meeting of the international society for the study of the lumbar spine
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] コバルトクロムnotch-freeプリベントロッドは脊柱変形矯正手術に有用である-曲げ加工法および金属材料における力学特性の検討-2019

    • Author(s)
      山田 勝久,須藤 英毅,岩崎 倫政,千葉 晶彦
    • Organizer
      第34回日本整形外科基礎学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 化膿性脊椎炎に対する早期からの広域抗菌薬長期投与は耐性菌の発生を助長する -後側方内視鏡下掻爬術114例の後ろ向き観察研究-2018

    • Author(s)
      山田 勝久,高畑 雅彦,長濱 賢,須藤 英毅,岩田 玲,遠藤 努,石黒信久,伊東 学,岩崎 倫政
    • Organizer
      第47回日本脊椎脊髄病学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 化膿性脊椎炎に対する早期からの広域抗菌薬長期投与は耐性菌の発生を助長する -後側方内視鏡下掻爬術114例の後ろ向き観察研究-2018

    • Author(s)
      山田 勝久,高畑 雅彦,長濱 賢,須藤 英毅,岩田 玲,遠藤 努,石黒信久,伊東 学,岩崎 倫政
    • Organizer
      第91回日本整形外科学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Prospective study of deep venous thrombosis associated with degenerative cervical spinal surgery2017

    • Author(s)
      3.Katsuhisa Yamada, Kota Suda, Satoko Matsumoto, Miki Komatsu, Chikara Ushiku, Masahiko Takahata
    • Organizer
      Annual Meeting of Cervical Spine Research Society -Asia Pacific Section-
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 思春期特発性側弯症(Lenke Type1)に対する前方矯正固定術の長期治療成績 -最上位固定椎の術後変位からの検討-2017

    • Author(s)
      山田勝久,須藤英毅,金田清志,庄野泰弘,安倍雄一郎,岩崎倫政
    • Organizer
      第46回日本脊椎脊髄病学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頚椎化膿性脊椎炎の臨床的特徴と機能予後 -後弯変形とQOLとの関連-2017

    • Author(s)
      山田勝久,高畑雅彦,須藤英毅,岩田玲,小甲晃史,岩崎倫政
    • Organizer
      第46回日本脊椎脊髄病学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 思春期特発性側弯症(Lenke Type1)に対する前方矯正固定術の長期治療成績 -最上位固定椎の術後変位からの検討-2017

    • Author(s)
      山田勝久,須藤英毅,金田清志,庄野泰弘,安倍雄一郎,岩崎倫政
    • Organizer
      第90回日本整形外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 急速な脊髄障害の進行は頚椎手術術後早期における深部静脈血栓症の危険因子である-380名のprospective study-2017

    • Author(s)
      山田勝久,須田浩太,松本聡子,小松幹,牛久智加良,東條泰明,三浪明男,高畑雅彦,岩崎倫政
    • Organizer
      第90回日本整形外科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 頚椎変性疾患周術期におけるD-dimer値と深部静脈血栓症の関連 -289例のprospective studyから-2017

    • Author(s)
      山田勝久,須田浩太,松本聡子,小松幹,高畑雅彦,三浪明男,岩崎倫政
    • Organizer
      第32回日本整形外科学会基礎学術総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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