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Elucidation of molecular mechanisms of Nrf2-mediated osteoclastogenesis and search of natural products as molecular targets

Research Project

Project/Area Number 25462892
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SAKAI Eiko  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (10176612)

Co-Investigator(Kenkyū-buntansha) TSUKUBA Takayuki  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (30264055)
OKAMOTO Kuniaki  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (10311846)
NISHISHITA Kazuhisa  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (20237697)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords破骨細胞 / 酸化ストレス / 天然物 / Nrf2 / 骨代謝 / osteoclast / keap1 / NFATc1 / c-Fos
Outline of Final Research Achievements

This study investigated the role of Keap1/Nrf2 axis in the differentiation of osteoclast using wild-type, Keap1-deficient, and Nrf2-deficient mice. Keap1-deficient osteoclast precursors showed defects in osteoclastogenesis through the inhibition of phosphorylation of ERK, P38 MAPK, and JNK. Furthermore, the protein expression of NFATc1 was significantly downregulated. In contrast, Nrf2-deficient osteoclast precursors underwent enhanced osteoclastogenesis through the activation of ERK, p38 MAPK, and JNK signaling. Moreover, nuclear translocation of NFATc1 and c-Fos was increased in Nrf2-deficient osteoclast precursors. However, microcomputed tomographic analyses and histological analyses of femurs with hematoxylin-eosin staining showed no significant defects among these mice. Furthermore, we compared the inhibitory effects of cafestol and kahweol, or sanguiin H-6 and its degradation product, ellagic acid on osteoclast differentiation.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (15 results)

All 2015 2014 2013

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Acknowledgement Compliant: 1 results) Presentation (12 results) Book (1 results)

  • [Journal Article] Dual Effects of Liquiritigenin on the Proliferation of Bone Cells : Promotion of Osteoblasl Differentiation and Inhibition of Osteoclast Differentiation2015

    • Author(s)
      Kaho Uchino, Kuniaki Okamoto, Eiko Sakai, Erika Yoneshima, Mayumi Iwatake, Yutaka Fukuma, Kazuhisa Nishishita and Takayuki Tsukuba
    • Journal Title

      PHYTOTHERAPY RESEARCH

      Volume: 11 Issue: 11 Pages: 1714-21

    • DOI

      10.1002/ptr.5416

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cafestol has a weaker inhibitory effect on osteoclastogenesis than kahweol and promotes osteoblast differentiation.2015

    • Author(s)
      Fukuma Y, Sakai E, Nishishita K, Okamoto K, Tsukuba T
    • Journal Title

      Biofactors

      Volume: 41 Issue: 4 Pages: 222-231

    • DOI

      10.1002/biof.1218

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Keap1/Nrf2 の破骨細胞と骨芽細胞分化における役割2015

    • Author(s)
      坂井詠子、福間裕、山口優、西下一久、岡元邦彰、筑波隆幸
    • Organizer
      第38回日本分子生物学会年会 第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートピアホテル・国際会議場(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Keap1/Nrf2 の破骨細胞分化における役割2015

    • Author(s)
      坂井詠子、福間裕、西下一久、岡元邦彰、筑波隆幸
    • Organizer
      第57回歯科基礎医学会
    • Place of Presentation
      朱鷺メッセ(新潟県・新潟市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] カフェストールは、カフェオールより破骨細胞分化阻害効果が弱く、骨芽細胞の成熟を促進する2015

    • Author(s)
      福間裕、坂井詠子、西下一久、岡元邦彰、筑波隆幸
    • Organizer
      第57回歯科基礎医学会
    • Place of Presentation
      朱鷺メッセ(新潟県・新潟市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] BMP 誘導骨芽細胞分化における転写因子 Transcription factor EB の役割2015

    • Author(s)
      米嶋えりか、岡元邦彰、 Wang Xiaobin、坂井詠子、西下一久、吉田教明、筑波隆幸
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] リクイリチゲニンの骨芽細胞および破骨細胞分化における影響2015

    • Author(s)
      岡元邦彰、内野加穂、米嶋えりか、坂井詠子、西下一久、筑波隆幸
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] Nrf2 遺伝子欠損マウスにおける酸化ストレスと骨代謝2014

    • Author(s)
      坂井詠子、山口優、福間裕、菅原めぐみ、西下一久、岡元邦彰、筑波隆幸
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Rab27Aは破骨細胞の多核化とリソソーム機能を制御する2014

    • Author(s)
      菅原めぐみ、坂井詠子、福間裕、西下一久、岡元邦彰、福田光則、泉哲郎、吉田教明、筑波隆幸
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都国際会館(京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Nrf2 遺伝子欠損マウスにおける酸化ストレスと破骨細胞分化2014

    • Author(s)
      坂井詠子、福間裕、菅原めぐみ、西下一久、岡元邦彰、筑波隆幸
    • Organizer
      第56回歯科基礎医学会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 破骨細胞の多核化とリソソーム機能を制御するrabタンパク質の同定2014

    • Author(s)
      菅原めぐみ、坂井詠子、福間裕、西下一久、岡元邦彰、吉田教明、筑波隆幸
    • Organizer
      第56回歯科基礎医学会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] Chemical constituents of Sanguisorba officinalis inhibits osteoclastogenesis2014

    • Author(s)
      坂井詠子、岩竹真弓、福間裕、西下一久、岡元邦彰、田中隆、筑波隆幸
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      宮城県仙台市仙台国際センター
    • Related Report
      2013 Research-status Report
  • [Presentation] Nrf2欠損は破骨細胞分化を促進する2013

    • Author(s)
      坂井詠子、福間裕、菅原めぐみ、西下一久、岡元邦彰、筑波隆幸
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      神奈川県横浜市パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Sanguisorba officinalis 由来化学成分の破骨細胞分化に対する影響2013

    • Author(s)
      坂井詠子、岩竹真弓、西下一久、福間裕、岡元邦彰、筑波隆幸
    • Organizer
      第55回歯科基礎医学会
    • Place of Presentation
      岡山県岡山市岡山コンベンションセンター
    • Related Report
      2013 Research-status Report
  • [Book] COFFEE IN HEALTH AND DISEASE PREVENTION (Chapter 96 を担当)2015

    • Author(s)
      Eiko Sakai, Takayuki Tsukuba
    • Publisher
      Academic Press (edited by Victor R. Preedy)
    • Related Report
      2014 Research-status Report

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

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