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Role of Osteocytes in Phosphate Sensing and Its Relation to Skeletal Maturation

Research Project

Project/Area Number 18K07838
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionOsama Woman's and Children's Hospital

Principal Investigator

Michigami Toshimi  地方独立行政法人大阪府立病院機構大阪母子医療センター(研究所), 骨発育疾患研究部門(旧環境影響部門), 部長 (00301804)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsリン代謝 / 骨細胞 / 骨芽細胞分化 / 骨成熟 / リン
Outline of Final Research Achievements

Using mouse models, we have investigated the relation between the skeletal maturation and alteration in phosphate metabolism during growth period. The bones of adult mice contained more abundant FGF23 protein than those of young mice. However, the expression of other analyzed molecules related to phosphate metabolism and osteoblastic differentiation was stronger in the osteoblasts and osteocytes derived from young mice than those from adult mice, and they were also up-regulated in the osteoblasts and osteocytes from a mouse model of hypophosphatemic rickets. The renal expression of Cyp24a1 was lower, and that of Slc34a3 was higher, in the younger mice than in the adult mice, which might suggest a weaker action of FGF23 and might contribute to the increase of phosphate in the body during growth period.

Academic Significance and Societal Importance of the Research Achievements

成長期にはリンの需要が高まり、リンの不足はくる病などの代謝性骨疾患や成長障害をきたすため、小児医療においてリン代謝の理解は重要である。本研究により、成長に伴って骨芽細胞や骨細胞におけるリン代謝や石灰化に関わる分子群の発現やリン酸応答性が変化することが明らかになった。また、低リンくる病の病態形成に骨芽細胞・骨細胞の成熟障害が関連していることが示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels2020

    • Author(s)
      Masanobu Kawai, Saori Kinoshita, Keiichi Ozono, Toshimi Michigami
    • Journal Title

      Scientific Reports

      Volume: 10(1) Issue: 1 Pages: 21501-21501

    • DOI

      10.1038/s41598-020-78692-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term outcomes for Asian patients with X-linked hypophosphataemia: rationale and design of the SUNFLOWER longitudinal, observational cohort study2020

    • Author(s)
      Kubota Takuo、Fukumoto Seiji、Cheong Hae Il、Michigami Toshimi、Namba Noriyuki、Ito Nobuaki、Tokunaga Shin、Gibbs Yoshimi、Ozono Keiichi
    • Journal Title

      BMJ Open

      Volume: 10 Issue: 6 Pages: e036367-e036367

    • DOI

      10.1136/bmjopen-2019-036367

    • NAID

      120006953549

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Skeletal mineralization: mechanisms and diseases.2019

    • Author(s)
      Michigami Toshimi
    • Journal Title

      Annals of Pediatric Endocrinology & Metabolism

      Volume: 24 Issue: 4 Pages: 213-219

    • DOI

      10.6065/apem.2019.24.4.213

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of Phosphate in Skeleton2019

    • Author(s)
      Michigami Toshimi、Ozono Keiichi
    • Journal Title

      Frontiers in Endocrinology

      Volume: 10 Pages: 180-180

    • DOI

      10.3389/fendo.2019.00180

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phosphate as a Signaling Molecule and Its Sensing Mechanism.2018

    • Author(s)
      Michigami T, Kawai M, Yamazaki M, Ozono K
    • Journal Title

      Physiol Rev

      Volume: 98 Issue: 4 Pages: 2317-2348

    • DOI

      10.1152/physrev.00022.2017

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 骨芽細胞機能におけるIII型ナトリウム/リン酸共輸送担体の役割2020

    • Author(s)
      山﨑美和, 川井正信, 大薗恵一, 道上敏美.
    • Organizer
      第93回日本内分泌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] III型ナトリウム/リン酸共輸送担体は骨石灰化およびピロリン酸・ATP代謝を制御する2020

    • Author(s)
      山﨑美和, 川井正信, 木下さおり, 大薗恵一, 道上敏美
    • Organizer
      第22回日本骨粗鬆症学会/第37回日本骨代謝学会学術集会合同集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Skeletal Mineralization: Mechanisms and Diseases.2019

    • Author(s)
      Michigami Toshimi
    • Organizer
      45th Annual Congress of Korean Society of Pediatric Endocrinology
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Functional control of osteoblasts by type III sodium/phosphate cotransporters.2019

    • Author(s)
      Yamazaki Miwa, Kawai Masanobu, Ozono Keiichi, Michigami Toshimi
    • Organizer
      42nd Annual meeting of the American Society for Bone and Mineral Research.
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 病態から理解する、くる病と骨軟化症の診断と治療.2019

    • Author(s)
      道上敏美
    • Organizer
      第29回 臨床内分泌代謝Update
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] リンの恒常性維持とシグナル分子としてのリン2018

    • Author(s)
      道上敏美
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 骨格の石灰化機構とその破綻による種々の病態2018

    • Author(s)
      道上敏美
    • Organizer
      第36回内分泌代謝学サマーセミナー
    • Related Report
      2018 Research-status Report
  • [Presentation] 低リン血症性くる病と骨軟化症―病態から抗FGF23抗体による新規治療までー2018

    • Author(s)
      道上敏美
    • Organizer
      第28回日本内分泌学会臨床内分泌代謝Update
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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