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A therapeutic approach to bone diseases by regulating osteoblast differentiation

Research Project

Project/Area Number 26462817
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)
柿元 協子  鹿児島大学, 医歯学域歯学系, 助教 (40274849)
坂東 健二郎  明海大学, 歯学部, 講師 (50347093)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords骨代謝 / 骨芽細胞 / 細胞内シグナル伝達 / 細胞分化 / JNK / オステオポンチン / オステオカルシン / 幹細胞 / 口腔生化学 / 軟骨細胞 / サイトカイン / ケモカイン / メカニカルストレス
Outline of Final Research Achievements

Osteopontin (OPN) is osteogenic marker protein which have regulatory effects on inflammatory diseases and bone metabolic disorders. Inhibition of JNK significantly inhibited osteogenic differentiation characterized by matrix mineralization and the gene expression of osteocalcin (OCN), whereas it increased OPN expression, indicating two types of osteogenic differentiation: OCN secretion type and OPN secretion type. The appearance of OPN type was decreased in DUSP16, a JNK specific phosphatase, knockout mouse. Gene expression analysis using DNA microarray revealed that OPN type osteoblasts specifically express secretory proteins and some surface markers. Moreover, inhibitor of differentiation 4 (Id4) suppressed the inhibitory effect of Hey1 on OPN promoter activity and regulated the induction of OPN type osteoblasts. Our findings suggested that JNK signaling regulates multifunctional differentiation of OPN and OCN type osteoblasts.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (25 results)

All 2017 2016 2015 2014

All Journal Article (8 results) (of which Peer Reviewed: 6 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (17 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [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
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hepatocyte growth Factor reduces CXCL10 expression in keratinocytes.2016

    • Author(s)
      Hisadome M., Ohnishi T., Kakimoto K, Kusuyama J., Bandow K., Kanekura T., Matsuguchi T.
    • Journal Title

      FEBS Letters

      Volume: 590 Issue: 20 Pages: 3595-3605

    • DOI

      10.1002/1873-3468.12452

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] CXCL3 positively regulates adipogenic differentiation.2016

    • Author(s)
      Kusuyama J., Komorizono A., Bandow K., Ohnishi T., Matsuguchi T.
    • Journal Title

      J. Lipid. Res.

      Volume: 57 Issue: 10 Pages: 1806-1820

    • DOI

      10.1194/jlr.m067207

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Low-Intensity Pulsed Ultrasound (LIPUS) Stimulation Helps to Maintain the Differentiation Potency of Mesenchymal Stem Cells by Induction in Nanog Protein Transcript Levels and Phosphorylation.2016

    • Author(s)
      Kusuyama J., Hwan Seong C., Bandow K., Ohnishi T., Matsuguchi T.
    • Journal Title

      J. Orthop. Trauma

      Volume: 30 Issue: 8 Pages: S4-S5

    • DOI

      10.1097/01.bot.0000489983.17459.0b

    • Related Report
      2016 Annual Research Report
    • Open Access
  • [Journal Article] 骨再生のキープレイヤー2016

    • Author(s)
      松口徹也
    • Journal Title

      TEETHFUL

      Volume: 129 Pages: 9-11

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Induction of CXCL2 and CCL2 by pressure force requires IL-1-MyD88 axis in osteoblasts2015

    • Author(s)
      A Maeda, K Bandow, J Kusuyama, K Kakimoto, T Ohnishi, S Miyawaki, T Matsuguchi
    • Journal Title

      BONE

      Volume: 74 Pages: 76-82

    • DOI

      10.1016/j.bone.2015.01.007

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] AMP-activated protein kinase (AMPK) activity negatively regulates chondrogenic differentiation.2014

    • Author(s)
      Bandow K, Kusuyama J, Kakimoto K, Ohnishi T, Matsuguchi T.
    • Journal Title

      Bone.

      Volume: 2015 Pages: 125-33

    • DOI

      10.1016/j.bone.2014.12.001

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Low Intensity Pulsed Ultrasound (LIPUS) Influences the Multilineage Differentiation of Mesenchymal Stem and Progenitor Cell Lines through ROCK-Cot/Tp12-MEK-ERK Signaling Pathway2014

    • Author(s)
      Kusuyama J, Bandow K, Shamoto M, Kakimoto K, Ohnishi T, Matsuguchi T
    • Journal Title

      the Journal of Biological Chemistry

      Volume: 289 Issue: 15 Pages: 10330-10344

    • DOI

      10.1074/jbc.m113.546382

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 低出力超音波(LIPUS)による歯根膜由来幹細胞のBMP9誘導性骨分化及び炎症性応答の制御2017

    • Author(s)
      楠山譲二、中村利明、大西智和、榮樂菜保子、野口和行、松口徹也
    • Organizer
      第20回超音波骨折治療研究会
    • Place of Presentation
      品川インターシティホール(品川区・東京都)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低出力超音波刺激 (LIPUS) は骨芽細胞のLPS誘導性炎症反応を抑制する2016

    • Author(s)
      中尾寿奈、楠山譲二、田沼順一、松口徹也
    • Organizer
      第4回超音波分子診断治療研究会
    • Place of Presentation
      福岡
    • Year and Date
      2016-03-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 低出力超音波(LIPUS)による歯根膜由来幹細胞のBMP9誘導性骨分化及び炎症性応答の制御2016

    • Author(s)
      楠山譲二、中村利明、大西智和、榮樂菜保子、野口和行、松口徹也
    • Organizer
      第15回日本超音波治療研究会
    • Place of Presentation
      東京女子医科大学 (新宿区・東京都)
    • Related Report
      2016 Annual Research Report
  • [Presentation] BMP9はWnt非依存的に骨芽細胞のGSK3b/b-cateninシグナルを活性化する2016

    • Author(s)
      松口徹也、榮樂菜保子、楠山譲二、大西智和
    • Organizer
      第58回歯科基礎医学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市・北海道)
    • Related Report
      2016 Annual Research Report
  • [Presentation] JNKシグナリングは骨芽細胞の多様性分化を制御する2016

    • Author(s)
      楠山譲二、大西智和、松口徹也
    • Organizer
      第58回歯科基礎医学会
    • Place of Presentation
      札幌コンベンションセンター(札幌市・北海道)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 低出力超音波(LIPUS)は歯根膜由来幹細胞のBMP9誘導性骨分化を促進し炎症応答を防ぐ2016

    • Author(s)
      楠山譲二、中村利明、大西智和、榮樂菜保子、野口和行、松口徹也
    • Organizer
      第25回硬組織再生生物学会
    • Place of Presentation
      日本大学歯学部(千代田区・東京都)
    • Related Report
      2016 Annual Research Report
  • [Presentation] JNKシグナリングは骨芽細胞の多様性分化を制御する2016

    • Author(s)
      楠山譲二、大西智和、松口徹也
    • Organizer
      第34回日本骨代謝学会
    • Place of Presentation
      大阪国際会議場(大阪市・大阪府)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Dynamic regulation of bone metabolism2016

    • Author(s)
      Matsuguchi T.
    • Organizer
      Professional Talk Series
    • Place of Presentation
      Selangor, Malaysia
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ケモカインCXCL3は脂肪分化を促進する2016

    • Author(s)
      楠山譲二、小森園杏奈、坂東健二郎、大西智和、松口徹也
    • Organizer
      平成28年度日本生化学会九州支部例会
    • Place of Presentation
      鹿児島大学(鹿児島県・鹿児島市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] 骨芽細胞分化によるATP産生経路の呼吸鎖から解糖系への移行2015

    • Author(s)
      大西智和、楠山譲二、坂東健二郎、柿元協子、松口徹也
    • Organizer
      第88回日本生化学会大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] 圧刺激による骨芽細胞のケモカインの発現誘導にはIL-1βとMyD88シグナル伝達系が必要である2015

    • Author(s)
      前田綾,坂東健二郎,宮脇正一,松口徹也
    • Organizer
      第74回日本矯正歯科学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
  • [Presentation] p46JNK2 の構成的活性は脂肪分化前期におけるC/EBPδの発現に必須である2015

    • Author(s)
      楠山譲二、坂東健二郎、大西智和、仙波伊知郎、松口徹也
    • Organizer
      第57回歯科基礎医学会
    • Place of Presentation
      新潟
    • Year and Date
      2015-09-11
    • Related Report
      2015 Research-status Report
  • [Presentation] LIPUS(低出力超音波)による間葉系幹細胞の分化能維持2015

    • Author(s)
      楠山譲二、仙波伊知郎、松口徹也
    • Organizer
      第24回硬組織再生生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2015-08-22
    • Related Report
      2015 Research-status Report
  • [Presentation] LIPUS による間葉系幹細胞の未分化能の維持2015

    • Author(s)
      楠山譲二、成昌ファン、坂東健二郎、柿元協子、大西智和、松口徹也
    • Organizer
      第18回超音波骨折治療研究会
    • Place of Presentation
      兵庫 ANAクラウンプラザホテル神戸
    • Year and Date
      2015-01-17
    • Related Report
      2014 Research-status Report
  • [Presentation] 軟骨細胞分化におけるAMP-activated kinaseの役割2014

    • Author(s)
      坂東健二郎、楠山譲二、大西智和、柿元協子、松口徹也
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      神奈川 パシフィコ横浜
    • Year and Date
      2014-11-25
    • Related Report
      2014 Research-status Report
  • [Presentation] 脂肪細胞によって分泌されるケモカインCXCL3は脂肪分化を促進する2014

    • Author(s)
      楠山譲二、松口徹也
    • Organizer
      第35回日本肥満学会
    • Place of Presentation
      宮崎 フェニックスシーガイア コンベンションセンター
    • Year and Date
      2014-10-24 – 2014-10-25
    • Related Report
      2014 Research-status Report
  • [Presentation] オステオポンチンはLMW-PTPを介して骨芽細胞の生理的応答性に影響を与える2014

    • Author(s)
      楠山譲二、坂東健二郎、大西智和、仙波伊知郎、松口徹也
    • Organizer
      第56回歯科基礎医学会
    • Place of Presentation
      福岡 福岡国際会議場
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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