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Role of type III sodium/phosphate co-transporters in osteoblast differentiation and mineralization

Research Project

Project/Area Number 18K07866
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

Yamazaki Miwa  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), 流動研究員 (50455549)

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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsリン / Pit1 / Pit2 / 骨芽細胞 / Ⅲ型ナトリウム-リン酸共輸送担体
Outline of Final Research Achievements

In skeletons, extracellular phosphate (Pi) exerts various actions. Although these multiple actions of extracellular Pi on the skeletal cells are likely to be partly mediated by type III sodium/phosphate co-transporters Pit1 and Pit2, the details still remain unclear. In the current study, we generated osteoblastic cells lacking Pit1 or Pit2 by applying CRISPR/Cas9 genome editing. Our results demonstrated that ablation of Pit1 or Pit2 in the osteoblastic cell line led to accelerated mineralization, suppressed tissue-nonspecific alkaline phosphatase and altered the levels of extracellular and intracellular pyrophosphate and adenosine triphosphate, and we speculate that these changes might be partly mediated by changes in the availability of extracellular Pi.

Academic Significance and Societal Importance of the Research Achievements

近年、血管や脳などの異所性の石灰化におけるPit1やPit2の関与が報告され、注目を浴びている。しかしながら、小児の成長に関わる骨芽細胞の分化や石灰化におけるPit1およびPit2の生理的な機能については充分な検討がなされておらず、本研究の学術的意義は大きい。

Report

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

    (12 results)

All 2020 2019 2018 Other

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Remarks (3 results)

  • [Journal Article] Hypophosphatasia in Japan: ALPL Mutation Analysis in 98 Unrelated Patients2020

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

      Calcif Tissue Int

      Volume: 106 Issue: 3 Pages: 221-231

    • DOI

      10.1007/s00223-019-00626-w

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CREB activation in hypertrophic chondrocytes is involved in the skeletal overgrowth in epiphyseal chondrodysplasia Miura type caused by activating mutations of natriuretic peptide receptor B.2019

    • Author(s)
      Yamamoto K, Kawai M, Yamazaki M, Tachikawa K, Kubota T, Ozono K, Michigami T.
    • Journal Title

      Hum Mol Genet

      Volume: 28 Issue: 7 Pages: 1183-1198

    • DOI

      10.1093/hmg/ddy428

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intestinal clock system regulates skeletal homeostasis.2018

    • Author(s)
      Kawai M, Kinoshita S, Yamazaki M, Yamamoto K, Rosen CJ, Shimba S, Ozono K, Michigami T.
    • Journal Title

      JCI Insight

      Volume: 7 Issue: 5

    • DOI

      10.1172/jci.insight.121798

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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] 骨芽細胞機能制御における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集会
    • 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)
      山崎美和、川井正信、木下さおり、大薗恵一、道上敏美.
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] III型ナトリウム/リン酸共輸送担体を介する骨芽細胞機能制御2019

    • Author(s)
      山﨑美和, 川井正信,大薗恵一,道上敏美.
    • Organizer
      第37回日本骨代謝学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Functional Control of Osteoblasts by Type III Sodium/Phosphate Cotransporters.2019

    • Author(s)
      Yamazaki M, Kawai M, Ozono T, Michigami.
    • Organizer
      ASBMR 2019 Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 基質小胞性石灰化および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2018

    • Author(s)
      山崎美和、川井正信、大薗恵一、道上敏美
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] 研究内容 骨発育疾患研究部門(旧 環境影響部門)大阪母子医療センター【研究所】

    • URL

      https://www.wch.opho.jp/research/bone/content.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 研究内容 骨発育疾患研究部門 (旧 環境影響部門) 大阪母子医療センター【研究所】

    • URL

      https://www.wch.opho.jp/research/bone/content.html

    • Related Report
      2019 Research-status Report
  • [Remarks] 研究内容 環境影響部門 大阪母子医療センター[研究所]

    • URL

      https://www.wch.opho.jp/research/bone/content.html

    • Related Report
      2018 Research-status Report

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

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