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Analysis of cellular hierarchy in the periodontal ligament

Research Project

Project/Area Number 19H03830
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionOsaka University

Principal Investigator

Iwayama Tomoaki  大阪大学, 歯学研究科, 助教 (80757865)

Co-Investigator(Kenkyū-buntansha) 竹立 匡秀  大阪大学, 歯学部附属病院, 講師 (60452447)
村上 伸也  大阪大学, 歯学研究科, 教授 (70239490)
山下 元三  大阪大学, 歯学部附属病院, 講師 (90524984)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywords歯根膜 / 組織幹細胞 / シングルセル解析 / ノックインマウス / 系譜解析 / 歯周組織 / 幹細胞 / セメント芽細胞 / 組織再生 / 細胞系譜 / 運命決定 / trajectory / ヒエラルキー / RNA Velocity
Outline of Research at the Start

歯周病で失われた歯周組織を効果的に再生するためには、歯根膜中の間葉系幹細胞(MSC)が、様々な機能を持った細胞へと分化する過程を効率よく活性化することが重要である。しかしながら、歯根膜中のMSCを中心とした細胞構成やその分化過程については未だ不明な点が多い。そこで、マウス遺伝学を用いた細胞系譜解析やシングルセル解析を用いて、歯根膜の細胞構成やMSCがどのように様々な機能を持った細胞へと分化していくかの詳細を正しく理解するとともに、同分化過程を制御する因子を探索する。同因子の制御により、歯根膜MSCの分化制御が可能となり、予知性の高い歯周組織再生療法の開発にも繋がる基盤情報を構築する。

Outline of Final Research Achievements

Periodontal tissue stem cells in the periodontal ligament have been shown to play a major role in periodontal tissue homeostasis and regeneration. However, the detailed mechanism remains unclear. In this study, we developed a novel knock-in mouse and a cell isolation method to analyze the periodontal ligament. We then achieved a single-cell analysis of periodontal ligament cells, clarified the cellular composition and cell hierarchy, and identified Zbp1 as a regulator of cell differentiation.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、歯根膜に含まれる細胞群の全貌や、歯周組織の恒常性維持や再生機構の理解が進展したことにより、歯根膜組織幹細胞の分化制御を標的とした、予知性の高い歯周組織再生療法の開発にも繋がる基盤情報が得られた。この過程で開発した手法やマウスは歯周病の病態理解やその分子機構の解明にも広く応用可能と考えられる。これらの研究が進展することで、国民の健康とQuality of Life増進に寄与するものと期待できる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (21 results)

All 2021 2020 2019

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (19 results) (of which Int'l Joint Research: 8 results,  Invited: 3 results)

  • [Journal Article] Zbp1-positive cells are osteogenic progenitors in periodontal ligament2021

    • Author(s)
      Ueda Tsugumi、Iwayama Tomoaki、Tomita Kiwako、Matsumoto Shuji、Iwashita Mizuho、Bhongsatiern Phan、Sakashita Hiromi、Fujihara Chiharu、Takedachi Masahide、Murakami Shinya
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 7514-7514

    • DOI

      10.1038/s41598-021-87016-1

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteoblastic lysosome plays a central role in mineralization2019

    • Author(s)
      Iwayama Tomoaki、Okada Tomoko、Ueda Tsugumi、Tomita Kiwako、Matsumoto Shuji、Takedachi Masahide、Wakisaka Satoshi、Noda Takeshi、Ogura Taku、Okano Tomomichi、Fratzl Peter、Ogura Toshihiko、Murakami Shinya
    • Journal Title

      Science Advances

      Volume: 5 Issue: 7

    • DOI

      10.1126/sciadv.aax0672

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 定量解析を目的とした歯根膜からの細胞単離法の開発2021

    • Author(s)
      岩下瑞穂, 岩山智明, 冨田貴和子, 松本修治, パーンポンサティアン, 阪下裕美, 竹立匡秀, 山田聡, 村上伸也
    • Organizer
      第64回春季日本歯周病学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 歯周組織におけるリンパ管の役割2021

    • Author(s)
      松本修治、岩山智明、阪下裕美、冨田貴和子、岩下瑞穂、Phan Bhongsatiern、村上伸也
    • Organizer
      第64回秋季日本歯周病学会学術大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Novel isolation method for quantitative analysis of periodontal ligament-derived cells2021

    • Author(s)
      Mizuho Iwashita, Tomoaki Iwayama, Kiwako Tomita, Shuji Matsumoto, Phan Bhongsatiern, Hiromi Sakashita, Masahide Takedachi, Satoru Yamada, Shinya Murakami
    • Organizer
      2021 IADR/AADR/CADR General Session & Exhibition
    • Related Report
      2021 Annual Research Report
  • [Presentation] Increased Lymphatic Vessels During Periodontal Tissue Repair2021

    • Author(s)
      Shuji Matsumoto, Tomoaki Iwayama, Kiwako Tomita, Mizuho Iwashita, Phan Bhongsatiern, Hiromi Sakashita, Masahide Takedachi, Shinya Murakami
    • Organizer
      2021 IADR/AADR/CADR General Session & Exhibition
    • Related Report
      2021 Annual Research Report
  • [Presentation] 歯周組織幹細胞源としての歯根膜2020

    • Author(s)
      村上伸也、岩山智明
    • Organizer
      第19回 日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 多色細胞系譜追跡法を用いた歯根膜前駆細胞のクローナル解析2020

    • Author(s)
      冨田貴和子,岩山智明,上田亜美,松本修治,岩下瑞穂,村上伸也
    • Organizer
      第63回 春季日本歯周病学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Stem cells/progenitors in periodontal ligament2020

    • Author(s)
      T. Iwayama
    • Organizer
      IADR-APR Young Researcher Forum
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 創傷治癒における歯根膜長期標識保持細胞の解析2020

    • Author(s)
      冨田貴和子、岩山智明、松本修治、岩下瑞穂、村上伸也
    • Organizer
      第63 秋季日本歯周病学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 歯根膜Gli1陽性細胞の系譜解析2020

    • Author(s)
      松本修治、岩山智明、冨田貴和子、岩下瑞穂、村上伸也
    • Organizer
      第63 秋季日本歯周病学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Characterization of the PLAP-1-GFP/CreER knock-in mouse2020

    • Author(s)
      Tomoaki Iwayama , Kiwako Tomita , Shuji Matusmoto , Mizuho Iwashita , Chiharu Fujihara , Masahide Takedachi , Satoru Yamada , Shinya Murakami
    • Organizer
      The 68th Annual Meeting of Japanese Association for Dental Research
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨芽細胞コミットメント制御因子の探索2019

    • Author(s)
      上田亜美、岩山智明、冨田貴和子、松本修治、村上伸也
    • Organizer
      第62回 春季日本歯周病学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 標識保持細胞の追跡による歯根膜間葉系幹細胞の同定2019

    • Author(s)
      冨田貴和子、岩山智明、上田亜美、松本修治、村上伸也
    • Organizer
      第62回 春季日本歯周病学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Analysis of periodontal ligament stem cells in vivo2019

    • Author(s)
      Iwayama T, Murakami S
    • Organizer
      The 9th Japan-Thailand-Korea Joint Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Chasing histone 2B-GFP label-retaining mesenchymal cells in periodontal ligament2019

    • Author(s)
      Tomita K, Iwayama T, Ueda T, Matsumoto S, Iwashita M, Murakami S
    • Organizer
      The 9th Japan-Thailand-Korea Joint Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analyzing matrix vesicles in mineral-forming cells2019

    • Author(s)
      Iwayama T, Murakami S
    • Organizer
      OKINAWA COLLOIDS 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Long-term Label-retaining Cells in Periodontal Ligament2019

    • Author(s)
      Tomita K, Iwayama T, Ueda T, Matsumoto S, Iwashita M, Murakami S
    • Organizer
      4th Meeting of the International Association for Dental Research Asia Pacific Region 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Role of Zbp1 on osteogenic commitment of periodontal ligament cells2019

    • Author(s)
      Ueda T, Iwayama T, Tomita K, Matsumoto S, Iwashita M, Takedachi M, Murakami S
    • Organizer
      98th General Session & Exhibition of the IADR
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 組織透明化技術を用いたマウス歯根膜の三次元観察2019

    • Author(s)
      松本修治、岩山智明、上田亜美、冨田貴和子、岩下瑞穂、村上伸也
    • Organizer
      第62回 秋季日本歯周病学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of osteogenic commitment factors in periodontal ligament2019

    • Author(s)
      T. Ueda, T. Iwayama, K. Tomita, S. Matsumoto, M. Takedachi, S. Murakami
    • Organizer
      2019 IADR GENERAL SESSION
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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