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Establishment of the treatment and pathophysiology based on the suppression of the intervertebral disc degeneration .

Research Project

Project/Area Number 25462289
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionUniversity of Toyama

Principal Investigator

Seki Shoji  富山大学, 大学院医学薬学研究部(医学), 助教 (00432112)

Co-Investigator(Kenkyū-buntansha) KAWAGUCHI YOSHIHARU  富山大学, 医学薬学研究部(医学), 准教授 (00262527)
MOTOMURA HIRAKU  富山大学, 附属病院, 助教 (50640827)
Co-Investigator(Renkei-kenkyūsha) TSUMAKI NORIYUKI  京都大学, iPS細胞研究所, 教授 (50303938)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsCILP / 腰椎椎間板 / トランスジェニックマウス / 脊椎脊髄病学 / AP-1阻害剤 / 椎間板穿刺モデル
Outline of Final Research Achievements

Safranin O staining in intervertebral disc were significantly decreased in Nucleus pulposus tissues of CILP Tg mice compared to controls. MRI analysis indicated obvious progression of degenerative intervertebral discs in Tg mice, which suggested reduction of the intensity of lumbar T2 weighted MR imaging.
We focused on the AP-1 of transcriptional factor which was therapeutic target for suppressing the intervertebral disc degeneration.AP-1 was expressed by MMP3, MMP13, ADAMTS4, and 5. An inhibitor of AP-1 was utilized by the experimental analysis of both in vitro and in vivo. This inhibitor was suppressed by the expression of both MMPs and ADAMTSs in in vitro. The intervertebral disc degeneration model which was induced by puncturing the intervertebral discs of mice tail was utilized by the in vivo analysis. An administration of the AP-1 inhibitor suppressed the intervertebral disc degeneration in this model.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (33 results)

All 2015 2014 2013

All Journal Article (12 results) (of which Peer Reviewed: 10 results,  Open Access: 2 results) Presentation (21 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Clinical significance of high intramedullary signal on T2-weighted cervical flexion-extension magnetic resonance imaging in cervical myelopathy.2015

    • Author(s)
      Seki S, Kawaguchi Y, Nakano M, Yasuda T, Hori T, Noguchi K, Kimura T.
    • Journal Title

      J Orthop Sci.

      Volume: 20 Issue: 6 Pages: 973-977

    • DOI

      10.1007/s00776-015-0757-x

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Circumferential Spinal Cord Decompression through a Single Posterior Approach with Microendoscopy for Thoracic and Thoracolumbar Ossification of the Posterior Longitudinal Ligament.2015

    • Author(s)
      Seki S, Mine H, Kawaguchi Y, Makino H, Kimura T.
    • Journal Title

      Asian Spine J.

      Volume: 9 Issue: 4 Pages: 605-611

    • DOI

      10.4184/asj.2015.9.4.605

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PCSK5 mutation in a patient with the VACTERL association2015

    • Author(s)
      Nakamura Y. et al.
    • Journal Title

      BMC Res Notes

      Volume: 8 Issue: 1 Pages: 228-228

    • DOI

      10.1186/s13104-015-1166-0

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the Alarm Criteria for Transcranial Electrical Stimulation Muscle Evoked Potential in Spinal Deformity Surgery:Multi-institution Survey by the Spinal Cord Monitoring Committee of the Japanese Society for Spine Surgery and Related Research2015

    • Author(s)
      Yamada K, Matsuyama Y, Kobayashi S, Nagahama K, Tadokoro N, Wada K, Muramoto A, Iwasaki H, Kanchiku T, Seki S, Hirao Y, Mizota A, Ando M, Yamamoto N, Kawabata S, Takahashi M, Ito Z, Fujiwara Y, Kida K, Tani T, Ohta R, Saito T, Satomi T, Shinomiya K.
    • Journal Title

      J. Spine Res.

      Volume: 6 Pages: 1354-1362

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monoparesis of upper extremity due to ipsilateral upper cervical cord compression: report of two cases.2015

    • Author(s)
      Kawaguchi Y, Yasuda T, Seki S, Hori T, Nakano M, Kimura T.
    • Journal Title

      J Orthop Sci.

      Volume: 20 Issue: 5 Pages: 939-942

    • DOI

      10.1007/s00776-014-0588-1

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mead acid (20:3n-9) and n-3 polyunsaturated fatty acids are not associated with risk of posterior longitudinal ligament ossification: results of a case-control study.2015

    • Author(s)
      Hamazaki K, Kawaguchi Y, Nakano M, Yasuda T, Seki S, Hori T, Hamazaki T, Kimura T.
    • Journal Title

      Prostaglandins Leukot Essent Fatty Acids.

      Volume: 96 Pages: 31-36

    • DOI

      10.1016/j.plefa.2015.01.003

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 成人脊柱変形に対する術前後テリパラチド投与の有用性について2015

    • Author(s)
      関 庄二, 川口善治, 中野正人, 安田剛敏, 平野典和, 木村友厚
    • Journal Title

      中部整災誌

      Volume: 58 Pages: 477-478

    • NAID

      130005092975

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Cartilage intermediate layer protein promotes lumbar disc degeneration.2014

    • Author(s)
      Seki S, Tsumaki N, Motomura H, Nogami M, Kawaguchi Y, Hori, T Suzuki K, Yahara Y, Higashimoto M, Oya T, Ikegawa S, Kimura T.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 446 Issue: 4 Pages: 876-881

    • DOI

      10.1016/j.bbrc.2014.03.025

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lumbar spinal stenosis due to a large calcified mass in the ligamentum flavum2013

    • Author(s)
      Seki S, Kawaguchi Y, Ishihara H, Oya T, Kimura T.
    • Journal Title

      Asian Spine Journal

      Volume: 7 Issue: 3 Pages: 236-241

    • DOI

      10.4184/asj.2013.7.3.236

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Relationship between postoperative axial symptoms and the rotationel angel of the cervical spine after laminoplasty2013

    • Author(s)
      Kawaguchi Y., Nogami S., Nakano M., Yasuda T., Seki S., Hori T., KimuraT
    • Journal Title

      European Journal of Orthopaedic Surgery & Traumatology

      Volume: 23 Issue: S1 Pages: 53-58

    • DOI

      10.1007/s00590-013-1219-9

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 特発性脊柱側弯症に対するuniplanar screwを用いたdirect vertebral rotation法による変形矯正2013

    • Author(s)
      関 庄二,中野正人,川口善治,峯 隼人,牧野紘士,安田剛敏,木村友厚
    • Journal Title

      整形外科

      Volume: 64 Pages: 94-99

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] 成人脊柱後側弯症に対する矯正固定術の固定下端について-L5固定下端の妥当性2013

    • Author(s)
      関 庄二,川口善治,中野正人,安田剛敏,堀 岳史,木村友厚
    • Journal Title

      中部日本整形外科災害外科学会雑誌

      Volume: 56 Pages: 1151-1152

    • NAID

      130004144053

    • Related Report
      2013 Research-status Report
  • [Presentation] 腰椎内視鏡下手術における手術高位の関節温存率の検討2015

    • Author(s)
      二川隼人,関 庄二、徳永綾乃,伊藤芳章, 木村友厚, 平野典和
    • Organizer
      第26回北陸脊椎脊髄外科研究会
    • Place of Presentation
      パレブラン高志会館(富山市)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] 変性側弯症を伴った腰部脊柱管狭窄症に対するOLIFと経皮的椎弓根スクリューを用いた矯正と間接的除圧の成績2015

    • Author(s)
      関 庄二, 川口善治, 安田剛敏, 鈴木賀代, 渡邉健太, 牧野紘士,金森昌彦, 木村友厚
    • Organizer
      第26回北陸脊椎脊髄外科研究会
    • Place of Presentation
      パレブラン高志会館(富山市)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] 特発性側弯症患者の後方矯正固定術におけるPonte osteotomyの意義について‐術中uni-planar screwを用いたデバイスでの測定-2015

    • Author(s)
      関 庄二, 川口善治, 中野正人, 安田剛敏, 牧野紘士,木村友厚
    • Organizer
      第26回北陸脊椎脊髄外科研究会
    • Place of Presentation
      パレブラン高志会館(富山市)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] 富山県におけるscoliometer を用いた検診での現状と問題点2015

    • Author(s)
      亀井克彦, 関 庄二, 川口善治, 安田剛敏, 牧野紘士, 中野正人, 木村友厚
    • Organizer
      第49回日本側弯症学会学術集会
    • Place of Presentation
      りゅーとぴあ 新潟市民芸術文化会館(新潟市)
    • Year and Date
      2015-11-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] 脊椎変形疾患における椎間板および黄色靭帯内のAGEs–AGEsは脊椎変形に関与するか.2015

    • Author(s)
      牧野紘士,川口善治,斎藤 充,関 庄二,安田剛敏,鈴木賀代,渡邉健太,木田吉城,丸毛啓史,木村友厚.
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場、富山市民プラザ(富山市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 変形性関節症性変化におけるSik3の役割.2015

    • Author(s)
      箭原康人,木村友厚,妻木範行.
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場、富山市民プラザ(富山市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 選択的c-Fos/AP-1阻害薬によるマウスの椎間板変性抑制効果.2015

    • Author(s)
      箭原康人,関 庄二,牧野紘士,塩沢俊一,妻木範行,木村友厚.
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場、富山市民プラザ(富山市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] ラット椎間板穿刺モデルを用いたc-Fos/A阻害薬の椎間板変形抑制効果.2015

    • Author(s)
      牧野紘士,関 庄二,元村 拓,箭原康人,野上真紀子,渡邉健太,塩沢俊一,木村友厚.
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場、富山市民プラザ(富山市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] Teriparatide versus bisphosphonates following surgery for adult spinal deformity in patients with osteoporosis2015

    • Author(s)
      Shoji Seki,Yoshiharu Kawaguchi, Masato Nakano, Taketoshi Yasuda, Hiroto Makino, Kayo Suzuki, and Tomoatsu Kimura
    • Organizer
      SRS 50th Annual Meeting & Course
    • Place of Presentation
      Hilton Minneapolis (アメリカ)
    • Year and Date
      2015-09-30
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] パーキンソン病に伴う腰椎変性側弯症に対して前後合併固定術後、隣接椎間障害を来した1例2015

    • Author(s)
      亀井克彦, 関 庄二, 川口善治, 安田剛敏, 鈴木賀代, 渡邉健太, 牧野紘士, 木村友厚
    • Organizer
      第200回北陸整形外科集談会
    • Place of Presentation
      金沢大学(金沢市)
    • Year and Date
      2015-09-13
    • Related Report
      2015 Annual Research Report
  • [Presentation] A dissociated effect after Ponte release for periapical segmental vertebral rotation in adolescent idiopathic scoliosis2015

    • Author(s)
      Shoji Seki, Yoshiharu Kawaguchi, Hiroto Makino, Tomoatsu Kimura
    • Organizer
      IMAST 2015
    • Place of Presentation
      KUALALUMPUR CONVENTION CENTER(マレーシア)
    • Year and Date
      2015-07-08
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 成人脊柱変形に対する術前後テリパラチド投与の有用性について.2015

    • Author(s)
      関 庄二, 川口善治, 中野正人, 安田剛敏, 鈴木賀代, 渡邊健太, 牧野紘士, 平野典和, 木村友厚
    • Organizer
      第88回日本整形外科学会学術総会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 特発性側弯症患者に対するDVRの意義について-術中CTによる椎体回旋改善度の測定から-.2015

    • Author(s)
      関 庄二, 川口善治, 中野正人, 安田剛敏, 鈴木賀代, 渡邊健太, 牧野紘士, 木村友厚
    • Organizer
      第87回日本整形外科学会学術総会
    • Place of Presentation
      神戸国際会議場(神戸市)
    • Year and Date
      2015-05-22
    • Related Report
      2015 Annual Research Report
  • [Presentation] 側彎症手術における脊髄モニタリングのアラームポイントの検討-日本脊椎脊髄病学会- 脊髄モニタリング委員会多施設研究の結果から-.2015

    • Author(s)
      山田 圭、小林 祥、関 庄二、田所伸朗、和田簡一郎、村本明生、岩崎 博、寒竹 司、平尾雄二郎、溝田敦子、安藤宗治、太田 亮、松山幸弘
    • Organizer
      第44 回日本脊椎脊髄病学会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] 特発性側弯症患者におけるApical Trunk Rotation(ATR)を改善させる因子の検討2013

    • Author(s)
      関 庄二,川口善治,中野正人,安田剛敏,峯 隼人,木村友厚
    • Organizer
      第47回日本側彎症学会
    • Place of Presentation
      ザ クラウンパレス新阪急高知(高知県高知市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 特発性側弯症患者に対するDVRの意義について-術中CTによる椎体回旋改善度の測定から-2013

    • Author(s)
      関 庄二,川口善治,中野正人,安田剛敏,峯 隼人,木村友厚
    • Organizer
      第47回日本側彎症学会
    • Place of Presentation
      ザ クラウンパレス新阪急高知(高知県高知市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 脊椎靭帯骨化症患者における全脊椎骨化巣の評価2013

    • Author(s)
      川口善治,中野正人,安田剛敏,関 庄二,堀 岳史,木村友厚
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      幕張メッセ(千葉県千葉市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 特発性側弯症患者に対するDVRの意義について-スクリュー長および径が椎体回旋におよぼす影響についての検討-.2013

    • Author(s)
      関 庄二,中野正人,川口善治,安田剛敏,堀 岳史,木村友厚
    • Organizer
      第86回日本整形外科学会学術総会
    • Place of Presentation
      広島グリーンアリーナ(広島県広島市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 頚髄症における頚椎前後屈MRIの有用性 -術後2年経過例について脊髄輝度変化と圧迫形態の検討-2013

    • Author(s)
      関 庄二、川口善治、中野正人、安田剛敏、堀 岳史、木村友厚
    • Organizer
      第42回日本脊椎脊髄病学会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 脊椎靭帯骨化症患者における全脊椎骨化巣の評価2013

    • Author(s)
      川口善治,中野正人,安田剛厳,関 庄二,堀 岳史,鈴木賀代,木村友厚
    • Organizer
      第42回日本脊椎脊髄病学会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 成人脊柱後側弯症に対する矯正固定術の固定下端について.-L5固定下端の妥当性-.2013

    • Author(s)
      関 庄二,川口善治,中野正人,安田剛敏,堀 岳史,木村友厚
    • Organizer
      第120回中部日本整形外科災害外科学会・学術集会
    • Place of Presentation
      和歌山県民文化会館(和歌山県和歌山市)
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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