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The roles of vitamin D dependent novel phosphate sensing-system on calcium metabolism and local calcification.

Research Project

Project/Area Number 26462816
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

MASUYAMA Ritsuko  長崎大学, 医歯薬学総合研究科(歯学系), 准教授 (60297596)

Co-Investigator(Kenkyū-buntansha) 小守 壽文  長崎大学, 医歯薬学総合研究科(歯学系), 教授 (00252677)
山中 仁木  長崎大学, 先導生命科学研究支援センター, 助教 (30533921)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsカルシウム輸送 / リン / 小腸 / 骨 / ビタミンD / カルシウム / ATP / 石灰化 / 恒常性 / ピロリン酸
Outline of Final Research Achievements

The impaired calcium absorption in intestinal Vdr null mice was improved by dietary phosphate restriction and resulted in increased bone mass, indicating that intestinal luminal phosphate levels influenced calcium absorption. Accordingly, transcellular calcium transport in cultured polarized intestinal epithelial cells was increased when apical side of cells were exposed to low extracellular phosphate levels (0.5 mM phosphate) compared to normal or high phosphate levels (1.0 and 5.0 mM). Mechanistically, low phosphate levels increased ATP contents at the apical extracellular side which stimulated the apical ATP receptor to promote calcium entry. The luminal ATP levels were regulated by the apical abundance of the ATP metabolizing enzyme, ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1). Sub-cellular localization of ENPP1 was reduced when apical side of intestinal epithelial cells were exposed to low extracellular phosphate, and led to the increase in luminal ATP levels.

Report

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

    (17 results)

All 2017 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (2 results)

  • [Journal Article] Methotrexate inhibits osteoclastogenesis by decreasing RANKL-induced calcium influx into osteoclast progenitors.2016

    • Author(s)
      Kanagawa H, Masuyama R, Morita M, Sato Y, Niki Y, Kobayashi T, Katsuyama E, Fujie A, Hao W, Tando T, Watanabe R, Miyamoto K, Morioka H, Matsumoto M, Toyama Y, Saya H, Miyamoto T.
    • Journal Title

      J Bone Miner Metab.

      Volume: 34 Issue: 5 Pages: 526-531

    • DOI

      10.1007/s00774-015-0702-2

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extra-intestinal calcium handling contributes to normal serum calcium levels when intestinal calcium absorption is suboptimal.2015

    • Author(s)
      Lieben L, Verlinden L, Masuyama R, Torrekens S, Moermans K, Schoonjans L, Carmeliet P, Carmeliet G.
    • Journal Title

      Bone

      Volume: 81 Pages: 502-512

    • DOI

      10.1016/j.bone.2015.08.023

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bone and Nutrition. Vitamin D independent calcium absorption.2015

    • Author(s)
      Masuyama R.
    • Journal Title

      Clin Calcium

      Volume: 25 Pages: 1023-1028

    • Related Report
      2015 Research-status Report
  • [Journal Article] Physiological functions of vitamin D: what we have learned from global and conditional VDR knockout mouse studies.2015

    • Author(s)
      Suda T, Masuyama R, Bouillon R, Carmeliet G.
    • Journal Title

      Curr Opin Pharmacol.

      Volume: 22 Pages: 87-99

    • DOI

      10.1016/j.coph.2015.04.001

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Identification and Characterization ofVancomycin-resistant <i>Enterococcus</i> species Frequently Isolated from Laboratory Mice2014

    • Author(s)
      Yamanaka H, Takagi T, Ohsawa M, Yamamoto N, Kubo N, Takemoto T, Sasano S, Masuyama R, Ohsawa K
    • Journal Title

      Experimental Animals

      Volume: 63 Issue: 3 Pages: 297-304

    • DOI

      10.1538/expanim.63.297

    • NAID

      130004677820

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of local vitamin D signaling and cellular calcium transport system in bone homeostasis.2014

    • Author(s)
      Masuyama R
    • Journal Title

      J. Bone Miner. Metab.

      Volume: 32 Issue: 1 Pages: 1-9

    • DOI

      10.1007/s00774-013-0508-z

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Vitamin D endocrine system and intestine.2014

    • Author(s)
      Christakos S, Lieben L, Masuyama R, Carmeliet G
    • Journal Title

      Bonekey reports

      Volume: 3 Pages: 1-6

    • DOI

      10.1038/bonekey.2013.230

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞内外のカルシウム恒常性と骨代謝制御2017

    • Author(s)
      増山律子
    • Organizer
      第122回 日本解剖学会
    • Place of Presentation
      長崎大学(長崎県・長崎市)
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 細胞外液リン量に応答する ATP依存性カルシウム吸収機構の検討2016

    • Author(s)
      増山律子
    • Organizer
      第70回 日本栄養食糧学会
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
  • [Presentation] Luminal phosphate regulates transcellular calcium transport in the intestinal epithelial cells.2016

    • Author(s)
      Ritsuko Masuyama, Hitoki Yamanaka, Liesbet Lieben, Geert Carmeliet, Kosei Ito
    • Organizer
      IBMS 2nd Herbert Fleisch workshop
    • Place of Presentation
      Brugge (Belgium)
    • Year and Date
      2016-02-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 活性型ビタミンDの生理作用と骨・カルシウム恒常性2015

    • Author(s)
      増山律子
    • Organizer
      第33回 日本骨代謝学会
    • Place of Presentation
      京王プラザホテル(新宿・東京)
    • Year and Date
      2015-07-23
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 骨の発達と機能を支えるビタミンの役割「ロコモティブシンドロームの基礎研究」2014

    • Author(s)
      増山律子
    • Organizer
      第69回日本体力医学会大会
    • Place of Presentation
      長崎大学(長崎市)
    • Year and Date
      2014-09-20
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 小腸上皮ATP分解系によるリン応答性経細胞カルシウム吸収調節機構の検討2014

    • Author(s)
      小原 悠, 増山律子
    • Organizer
      第32回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2014-07-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 局所でのビタミンDの作用と骨ミネラル代謝2014

    • Author(s)
      増山律子
    • Organizer
      第31回 長崎骨粗しょう症研究会
    • Place of Presentation
      長崎医師会館(長崎市)
    • Year and Date
      2014-07-16
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 小腸上皮ATP分解系によるカルシウム吸収調節機序の検討2014

    • Author(s)
      増山律子, 上川篤志, 小原悠, 山中仁木, 伊藤公成
    • Organizer
      第68回日本栄養・食糧学会大会
    • Place of Presentation
      酪農学園大学(札幌市)
    • Year and Date
      2014-05-30
    • Related Report
      2014 Research-status Report
  • [Book] The Bone2016

    • Author(s)
      増山律子
    • Total Pages
      6
    • Publisher
      メディカルレビュー社
    • Related Report
      2016 Annual Research Report
  • [Book] 骨代謝制御の分子メカニズムと骨代謝疾患の最新治療, 実験医学増刊号2014

    • Author(s)
      増山律子
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2014 Research-status Report

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

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