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The mechanism of BRONJ development by inflammation: The role of phosphate transporters as therapeutic target

Research Project

Project/Area Number 18K17111
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57050:Prosthodontics-related
Research InstitutionTohoku University

Principal Investigator

Kiyama Tomomi  東北大学, 東北メディカル・メガバンク機構, 助教 (40756011)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywordsビスホスホネート / 顎骨壊死 / トランスポーター
Outline of Final Research Achievements

The aim of this project was to investigate the pathogenesis of BRONJ, by elucidating the effect of inflammation on bisphosphonate’s cellular uptake, and the effect of bisphosphonate’s cytotoxicity on healing process after tooth extraction. As the results, phosphate transporter SLC34 may be associated with the bisphophonate’s cellular uptake and the transporter is increased with inflammation. Moreover, pre-administration of SLC 34 inhibitor suppress the BRONJ occurrence in vivo experiment. As to the effect of extraction site healing, granulation stage to angiogenic stage are the most affected.

Academic Significance and Societal Importance of the Research Achievements

当研究の研究結果により、現在すでにビスホスホネート製剤を投与されている患者に対しても、リン酸トランスポーター阻害剤の投与により、抜歯に付随して発症するBRONJを抑制できる可能性が示唆された。超高齢化に伴い、骨粗しょう症患者は増加しているため、ビスホスホネート製剤投与患者も増加している。そのため、本研究で得られた知見は、未だ確立していないBRONJの予防・治療方法の確立に大きく寄与すると考えられる。

Report

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

    (5 results)

All 2020 2019 Other

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

  • [Int'l Joint Research] Nova Southeastern University(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Nova Southeastern University(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] University of Michigan(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Basic Studies on the Mechanism, Prevention, and Treatment of Osteonecrosis of the Jaw Induced by Bisphosphonates2020

    • Author(s)
      Endo Yasuo、Funayama Hiromi、Yamaguchi Kouji、Monma Yuko、Yu Zhiqian、Deng Xue、Oizumi Takefumi、Shikama Yosuke、Tanaka Yukinori、Okada Satoshi、Kim Siyoung、Kiyama Tomomi、Bando Kanan、Shima Kazuhiro、Suzuki Hikari、Takahashi Tetsu
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 140 Issue: 1 Pages: 63-79

    • DOI

      10.1248/yakushi.19-00125

    • NAID

      130007778763

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2020-01-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Augmentation of Lipopolysaccharide-Induced Production of IL-1α and IL-1β in Mice Given Intravenous Zoledronate (a Nitrogen-Containing Bisphosphonate) and Its Prevention by Clodronate (a Non-nitrogen-containing Bisphosphonate)2019

    • Author(s)
      Suzuki H, Bando K, Tada H, Kiyama T, Oizumi T, Funayama H, Sugawara S, Takahashi T, Endo Y.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 2 Pages: 164-172

    • DOI

      10.1248/bpb.b18-00408

    • NAID

      130007588866

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-02-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

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Published: 2018-04-23   Modified: 2021-02-19  

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