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A novel regulation of farnesyl diphosphate synthase (FDPS) on the activity of Cl- extrusion in osteoclasts

Research Project

Project/Area Number 24592823
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Functional basic dentistry
Research InstitutionFukuoka Dental College

Principal Investigator

KAJIYA Hiroshi  福岡歯科大学, 歯学部, 講師 (80177378)

Co-Investigator(Kenkyū-buntansha) OKAMOTO Fujio  福岡歯科大学, 口腔歯学部, 講師 (60153938)
OKABE Koji  福岡歯科大学, 口腔歯学部, 教授 (80224026)
岡部 幸司  福岡歯科大学, 歯学部, 教授 (80224046)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords骨代謝 / 破骨細胞 / 酸分泌輸送体 / ビスホスホネート製剤 / 酸分泌 / メバロン酸経路 / ビスフォスフォネート製剤 / ファルネシル2リン酸合成酵素 / Clイオン輸送体 / Cl輸送体 / ファルネシル2リン酸合成酵素 / ビスフォスフォネート / 骨吸収
Outline of Final Research Achievements

Farnesyl diphosphate synthase (FDPS) have well known to be inhibited by nitrogen-containing bisphosphonates, leading to suppression of bone resorption in mature osteoclasts. However, little is known whether FDPS regulate directly the extrusion activity of ClC-7 Cl- transporters (ClC7) in mature osteoclasts. FDPS was associated and colocalized with ClC7 in mouse osteoclasts and HEK cells coexpressing FDPS and ClC7. Extracellular acidification induced outwardly rectifying Cl- currents (acid-induced Cl- currents) and decreased intracellular Cl- concentration ([Cl-]i) associated with ClC7 in osteoclasts. Zoledronic acid, FDPS inhibitors suppressed the acid-induced Cl- currents and [Cl-]i reduction. In transgenic mice overexpressing with FDPS (FDPS Tg-mice), bone mineral density significantly decreased with elevation of the bone resorption parameters. The results suggest that FDPS may contribute to regulate the bone resorption activity, especially the ClC7 activity in mature osteoclasts.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (26 results)

All 2015 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 2 results) Presentation (16 results) (of which Invited: 2 results) Book (1 results)

  • [Journal Article] Mevalonates restore zoledronic acid-induced osteoclastogenesis inhibition.2015

    • Author(s)
      Nagaoka Y, Kajiya H*, Ozeki S, Ikebe T, Okabe K
    • Journal Title

      J Dent Res.

      Volume: 94 Issue: 4 Pages: 594-601

    • DOI

      10.1177/0022034514564187

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Reactive oxygen species promotes cellular senescence in normal human epidermal keratinocytes through epigenetic regulation of p16(INK4a.).2015

    • Author(s)
      Sasaki M, Kajiya H*, Ozeki S, Okabe K, Ikebe T
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 452 Issue: 3 Pages: 622-628

    • DOI

      10.1016/j.bbrc.2014.08.123

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A novel inhibitory mechanism of nitrogen-containing bisphosphonate on theactivity of Cl- extrusion in osteoclasts.2013

    • Author(s)
      Ohgi, K., Kajiya, H., Okamoto, F., Nagaoka, Y., Onitsuka, T., Nagai, A., Sakagami, R., Okabe, K.
    • Journal Title

      Naunyn Schmiedebergs Arch Pharmacol

      Volume: (in press) Issue: 7 Pages: 589-598

    • DOI

      10.1007/s00210-013-0857-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The potential role of transient receptor potential type A1 as a mechanoreceptor in human periodontal ligament cells.2013

    • Author(s)
      Tsutsumi T, Kajiya H*, Fukawa T, Sasaki M, Nemoto T, Tsuzuki T, Takahashi Y, Fujii S, Maeda H, Okabe K.
    • Journal Title

      Eur J Oral Sci

      Volume: 121 Issue: 6 Pages: 538-544

    • DOI

      10.1111/eos.12083

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hyperocclusion up-regulates CCL3 expression in CCL2- and CCR2-deficient mice.2013

    • Author(s)
      Tsutsumi T, Kajiya H, Goto KT, Takahashi Y, Okabe K.
    • Journal Title

      J Dent Res. 2013 Jan;92(1):65-70.

      Volume: 92 Issue: 1 Pages: 65-70

    • DOI

      10.1177/0022034512467803

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reactive oxygen species stimulates epithelial mesenchymal transition in normal human epithelial keratinocytes via TGF-beta secretion.2012

    • Author(s)
      Fukawa T, Kajiya H, Ozeki S, Ikebe T, Okabe K.
    • Journal Title

      Exp Cell Res

      Volume: 318 Issue: 15 Pages: 1926-1932

    • DOI

      10.1016/j.yexcr.2012.05.023

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Odontoclasts and calcitonin2012

    • Author(s)
      Okabe K, Okamoto F, Kajiya H.
    • Journal Title

      Clin Calcium.

      Volume: 22 Pages: 19-26

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Calcium/calmodulin-signaling supports TRPV4 activation in osteoclasts and regulates bone mass.2012

    • Author(s)
      Masuyama R
    • Journal Title

      Journal of bone and mineral research

      Volume: 27 Issue: 8 Pages: 1708-1721

    • DOI

      10.1002/jbmr.1629

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] カーボンナノチューブによる温熱デバイスの構築と骨再生補助機材としての有用性の検討.、2012

    • Author(s)
      鍛治屋 浩*、堤 貴司、川口 稔
    • Journal Title

      福歯大雑誌

      Volume: 38 Pages: 145-151

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] カーボンナノチューブ(CNT)の発熱特性を利用した温熱付加による骨再生促進効果2015

    • Author(s)
      柳 束、鍛治屋浩、川口稔、勝俣由里、松本彩子、城戸寛史、福島忠男
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] DNA/プロタミン複合体による新生骨誘導作用機序の解明2015

    • Author(s)
      勝俣由里、鍛治屋浩、柳 束、大野純、川口稔、大関悟、池邊哲朗、福島忠男
    • Organizer
      第14回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2015-03-19 – 2015-03-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] 破骨細胞のイオン輸送体を介した分化・吸収過程の調節2015

    • Author(s)
      鍛治屋浩
    • Organizer
      第3回口腔神経科学研究会
    • Place of Presentation
      東京
    • Year and Date
      2015-02-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] DNA含有新規スカフォールド誘導性Na/PiIIb(SLC34b)の発現を介する新生骨形成2014

    • Author(s)
      勝俣由里、鍛治屋浩、柳束、大関悟、池邉哲郎、福島忠男
    • Organizer
      第7回トランスポーター研究会九州部会
    • Place of Presentation
      北九州
    • Year and Date
      2014-11-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 有病モデルラットにおけるDNA/プロタミン複合体の骨形成能の評価2014

    • Author(s)
      柳 束、森南奈、鍛治屋浩、大野純、城戸寛史、御手洗誠、早川徹、福島忠男
    • Organizer
      第36回日本バイオマテリアル学会
    • Place of Presentation
      千葉
    • Year and Date
      2014-11-17 – 2014-11-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] 窒素含有ビスホスホネート製剤(NBP)による破骨細胞の融合阻害を介する分化阻害作用2014

    • Author(s)
      長岡良礼、鍛治屋浩、岡本富士雄、福島秀文、岡部幸司
    • Organizer
      第32回日本骨代謝学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-24 – 2014-07-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] ビスホスホネート製剤による破骨細胞酸分泌輸送体の新しい調節機序2014

    • Author(s)
      鍛治屋浩
    • Organizer
      生体制御・創薬研究ワークショップin 鹿児島
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ファーネシル合成酵素による破骨細胞Cl-輸送体調節2014

    • Author(s)
      鍛治屋浩、大城希美子、岡本富士雄、岡部幸司
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島
    • Related Report
      2013 Research-status Report
  • [Presentation] The novel roles of CCL2 and CCL3 on osteoclast differentiation and alveolar bone resorption during occlusal traumatism.2013

    • Author(s)
      Tsutsumi T, Kajiya H, Goto K, Nagaoka Y, Okamoto F, Okabe K
    • Organizer
      2nd joint meeting of the international bone and mineral society and Japanease Society for bone and mineral Research
    • Place of Presentation
      Kobe, Japan
    • Related Report
      2013 Research-status Report
  • [Presentation] 窒素含有ビスホスホネート製剤(NBP)による破骨細胞の細胞融合阻害作用2013

    • Author(s)
      長岡良礼、鍛治屋浩、佐々木三奈、永沼香織、堤貴司、府川晃久、岡本富士雄、岡部幸司
    • Organizer
      第55回歯科基礎医学会総会
    • Place of Presentation
      岡山
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel role of farnesyl diphosphate synthase (FDPS) on the activity of Cl- extrusion in osteoclasts2013

    • Author(s)
      Kajiya H, Tsutsumi T, Nagaoka Y, Goto K, Fukawa T, Sasaki M, Okamoto F, Okabe K
    • Organizer
      American Society of Bone and Mineral Research 2013 Annual Meeting
    • Place of Presentation
      Baltimore, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Expression of C-C chemokine ligands for osteoclastogenesis induced by hyperocclusion2013

    • Author(s)
      Tsutsumi T, Kajiya H, Goto K, Takahashi Y, Okabe K
    • Organizer
      American Society of Bone and Mineral Research 2013 Annual Meeting
    • Place of Presentation
      Baltimore, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] マウス破骨細胞におけるMg2+抑制性TRPM7 様チャネルの性質2013

    • Author(s)
      岡本富士雄、鍛治屋浩、岡部幸司.
    • Organizer
      第90回日本生理学会
    • Place of Presentation
      千葉
    • Related Report
      2012 Research-status Report
  • [Presentation] CCL2シグナル欠損した咬合性外傷モデルマウスを用いた顎骨吸収時のケモカインの動態解析.2012

    • Author(s)
      堤貴司, 鍛治屋浩, 後藤加寿子, 岡部幸司.
    • Organizer
      第30回日本骨代謝学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 破骨細胞ClC7型Cl-輸送体(Clcn7)のファーネシル2リン酸合成酵素(Fdps)による活性化調節と阻害剤ゾレンドロン酸による新規骨吸収抑制作用機序.2012

    • Author(s)
      鍛治屋 浩、大城希美子、岡本富士雄、岡部幸司.
    • Organizer
      第30回日本骨代謝学会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] 窒素含有ビスフォスフォネ-ト (NBPs) は破骨細胞 Clcn7 を介してCl-輸送を抑制する.2012

    • Author(s)
      3. 大城希美子, 鍛治屋浩, 岡本富士雄, 堤貴司, 長岡良礼, 佐々木三奈, 坂上竜資, 岡部幸司.
    • Organizer
      第6回トランスポ-タ-研究会九州部会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Book] Advances in Experimental Medicine and Biology; Calcium signaling Chapter 41:Calcium signaling in osteoclast differentiation and bone2012

    • Author(s)
      Kajiya H
    • Total Pages
      1267
    • Publisher
      Springer press (Edited by Shahidul Islam)
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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