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Investigation of Novel isoform-specific signal transcution mechanisms of JNKs

Research Project

Project/Area Number 17K11646
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionKagoshima University

Principal Investigator

Matsuguchi Tetsuya  鹿児島大学, 医歯学域歯学系, 教授 (10303629)

Co-Investigator(Kenkyū-buntansha) 大西 智和  鹿児島大学, 医歯学域歯学系, 准教授 (30244247)
楠山 譲二  鹿児島大学, 医歯学総合研究科, 客員研究員 (70596105)
柿元 協子  鹿児島大学, 医歯学総合研究科, 客員研究員 (40274849)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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細胞分化 / 骨代謝 / 骨芽細胞 / 脂肪細胞 / 細胞内シグナル伝達 / 転写因子 / 骨形成タンパク質 / JNK / ホスファターゼ / キナーゼ / シグナル伝達 / アイソフォーム / 遺伝子発現 / 免疫応答 / 糖代謝
Outline of Final Research Achievements

JNK is known as a multifunctional kinase controling various biological functions. There are 3 isoforms (JNK1/2/3) of JNK. However, exact functional differences among these isoforms have not been fully elucidated. We have previously identified isoform-specific regulatory functions of JNK in osteoblast differentiation. Here, we have newly revealed 1) JNK2 specifically play essential roles in the early differentiation process of adipocyte diffrentiation, 2) Osteopontin-dominant type of osteoblast differentiation is induced by JNK inhibition via a transcriptional regulator, Id4, and 3) BMP9 negatively inhibits osteopontin-dominant differentiation of osteoblasts via inhibiting Id4.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、JNK活性がアイソフォーム特異的に、多分化能を持つ間葉系幹細胞から脂肪・骨細胞分化への制御に重要な働きをすること、また骨形成因子であるBMP9がそのプロセスに影響を与えることを明らかにした。本研究の成果は、超高齢化社会のQOL維持のために必須となってくる骨再生療法のよりよい臨床応用法の開発に繋がる重要な所見と考えられる。また、将来的には、JNKが発症に関与する炎症性疾患、糖尿病、がん、心血管障害などの疾患のより効率的な予防・治療法の開発に繋がることも期待される。

Report

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

    (22 results)

All 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 10 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (11 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] エアランガ大学(ミャンマー)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Low intensity pulsed ultrasound (LIPUS) maintains osteogenic potency by the increased expression and stability of Nanog through spleen tyrosine kinase (Syk) activation.2019

    • Author(s)
      Kusuyama J, Seong C, Makarewicz NS, Ohnishi T, Shima K, Semba I, Bandow K, Matsuguchi T.
    • Journal Title

      Cell Signal.

      Volume: 62 Pages: 109345-109345

    • DOI

      10.1016/j.cellsig.2019.109345

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] JNK inactivation suppresses osteogenic differentiation, but robustly induces osteopontin expression in osteoblasts through the induction of inhibitor of DNA binding 4 (Id4).2019

    • Author(s)
      Kusuyama J, Amir MS, Albertson BG, Bandow K, Ohnishi T, Nakamura T, Noguchi K, Shima K, Semba I, Matsuguchi T.
    • Journal Title

      FASEB J.

      Volume: - Issue: 6 Pages: 7331-7347

    • DOI

      10.1096/fj.201802465r

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Low-intensity pulsed ultrasound promotes bone morphogenic protein 9-induced osteogenesis and suppresses inhibitory effects of inflammatory cytokines on cellular responses via Rho-associated kinase 1 in human periodontal ligament fibroblasts.2019

    • Author(s)
      Kusuyama J, Nakamura T, Ohnishi T, Albertson BG, Ebe Y, Eiraku N, Noguchi K, Matsuguchi T.
    • Journal Title

      J Cell Biochem

      Volume: - Issue: 9 Pages: 14657-14669

    • DOI

      10.1002/jcb.28727

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BMP9 directly induces rapid GSK3-β phosphorylation in a Wnt-independent manner through class I PI3K-Akt axis in osteoblasts.2019

    • Author(s)
      Eiraku N, Chiba N, Nakamura T, Amir MS, Seong CH, Ohnishi T, Kusuyama J, Noguchi K, Matsuguchi T.
    • Journal Title

      FASEB Journal

      Volume: 33 Issue: 11 Pages: 12124-12134

    • DOI

      10.1096/fj.201900733rr

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CXCL13 is a differentiation- and hypoxia-induced adipocytokine that exacerbates the inflammatory phenotype of adipocytes through PHLPP1 induction.2019

    • Author(s)
      Kusuyama J, Bandow K, Ohnishi T, Amir MS, Shima K, Semba I, Matsuguchi T.
    • Journal Title

      Biochem J

      Volume: 476 Issue: 22 Pages: 3533-3548

    • DOI

      10.1042/bcj20190709

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] BMP9 prevents induction of osteopontin in JNK-inactivated osteoblasts via Hey1-Id4 interaction.2019

    • Author(s)
      Kusuyama J, Seong C, Nakamura T, Ohnishi T, Amir MS, Shima K, Semba I, Noguchi K, Matsuguchi T.
    • Journal Title

      Int J Biochem Cell Biol.

      Volume: 116 Pages: 105617-105617

    • DOI

      10.1016/j.biocel.2019.105614

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Spleen tyrosine kinase influences the early stages of multilineage differentiation of bone marrow stromal cell lines by regulating phospholipase C gamma activities.2018

    • Author(s)
      Kusuyama J,, Kamisono A, ChangHwan S, Amir MS, Bandow K, Eiraku N, Ohnishi T, Matsuguchi T.
    • Journal Title

      J Cell Physiol.

      Volume: 233 Issue: 3 Pages: 2549-2559

    • DOI

      10.1002/jcp.26130

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Osteopontin inhibits osteoblast responsiveness through the downregulation of focal adhesion kinase mediated by the induction of low molecular weight-protein tyrosine phosphatase.2017

    • Author(s)
      Kusuyama J., Bandow K., Ohnishi T., Hisadome M., Shima K., Semba I., Matsuguchi T.
    • Journal Title

      Mol. Biol. Cell.

      Volume: Mar 22 Issue: 10 Pages: 10-07

    • DOI

      10.1091/mbc.e16-10-0716

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Constitutive activation of p46JNK2 is indispensable for C/EBPδ induction in the initial stage of adipogenic differentiation.2017

    • Author(s)
      Kusuyama J, Ohnishi T, Bandow K, Amir MS, Shima K, Semba I, Matsuguchi T.
    • Journal Title

      Biochem J.

      Volume: 474 Issue: 20 Pages: 3421-3437

    • DOI

      10.1042/bcj20170332

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low-Intensity Pulsed Ultrasound (LIPUS) Promotes BMP9-Induced Osteogenesis and Suppresses Inflammatory Responses in Human Periodontal Ligament-Derived Stem Cells.2017

    • Author(s)
      Kusuyama J, Nakamura T, Ohnishi T, Eiraku N, Noguchi K, Matsuguchi T.
    • Journal Title

      J Orthop Trauma.

      Volume: 31 Issue: 7 Pages: S4-S4

    • DOI

      10.1097/01.bot.0000520897.92470.70

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Hes1 plays an important role in mediating BMP9-induced osteoblast differentiation2019

    • Author(s)
      Chang-Hwan Seong, Tetsuya Matsuguchi, Norifumi Nakamura
    • Organizer
      1st International Conference Brawijaya Dentistry
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Elucidation of molecular mechanisms and functional roles of Notch signaling molecule Hes1 in BMP9-induced osteoblast differentiation2019

    • Author(s)
      成 昌奐、 大西 智和、 千葉 紀香、 松口 徹也
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 解糖阻害は初期分化段階の初代骨芽細胞においてユビキチン-プロテアソーム系を介してアポトーシスタンパク質の発現を増加させる2019

    • Author(s)
      大西 智和 千葉 紀香 松口 徹也
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] BMP-9による骨芽細胞分化におけるEgr-1の役割の解析2019

    • Author(s)
      千葉 紀香、大西 智和、松口 徹也
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] BMP9 刺激によって誘導される Hif-1α は解糖系酵素 PDK1 の発現を介して骨芽細胞分化に必須の役割を果たす2019

    • Author(s)
      松口 徹也、千葉 紀香、成 昌奐、大西 智和
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] BMP9の骨芽細胞分化誘導作用におけるPI3K-Akt-GSK3b/b-cateninシグナル経路の重要性2018

    • Author(s)
      松口徹也、千葉紀香、楠山譲二、大西智和
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] クラミジア肺炎時の肺への免疫細胞の浸潤におけるマスト細胞の重要な役割2018

    • Author(s)
      千葉紀香、楠山譲二、大西智和、松口徹也
    • Organizer
      第60回歯科基礎医学会学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 骨芽細胞分化におけるBMP9の特異的シグナル伝達経路の解明2018

    • Author(s)
      榮樂菜保子、中村利明、野口和行、松口徹也
    • Organizer
      日本歯科保存学会2018年度秋季学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 骨形成タンパク質9(BMP9) 刺激骨芽細胞における Notch エフェクター分子 Hes1 の発現誘導機構および機能的意義2018

    • Author(s)
      成昌ファン,松口徹也,中村典史
    • Organizer
      第73回 日本口腔科学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ケラチノサイトにおける紫外線B波長によるインターフェロンγ反応性の阻害はERストレスを介する2018

    • Author(s)
      大西智和、千葉紀香、榮樂菜保子、スバン・アミール、松口徹也
    • Organizer
      第91回日本生化学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 解糖系阻害が骨芽細胞のユビキチンープロテアソーム機構に及ぼす影響2017

    • Author(s)
      大西智和、楠山讓二、榮楽菜穂子、スバン・アミール、松口徹也
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Research-status Report

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

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