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Development of a 3D gingival tissue model infected with periodontal pathogens and dynamic analysis of host invasion

Research Project

Project/Area Number 20K12646
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionOsaka University

Principal Investigator

Sasaki Naoko  大阪大学, 大学院工学研究科, 特任研究員(常勤) (10388762)

Co-Investigator(Kenkyū-buntansha) 松崎 典弥  大阪大学, 大学院工学研究科, 教授 (00419467)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords三次元歯肉モデル組織 / Porphyromonas gingivalis / 血管網構造 / コラーゲンマイクロファイバー (CMF) / 歯周病菌感染歯肉モデル組織 / P. gingivalis / 上皮細胞層 / ジンジパイン / 上皮バリア
Outline of Research at the Start

歯周病は動脈硬化症や糖尿病など、様々な疾患の発症や悪化に関与している。歯周病菌は歯茎の血管から侵入し、全身へ運ばれると考えられているが、感染の初期メカニズムは、殆ど判っていない。本研究では、結合組織層に血管網構造を有する生体に近い3次元歯肉モデル組織に歯周病の代表的原因菌であるPorphyromonas gingivalisを感染させ、歯肉上皮バリアを突破するメカニズムの解明を目的とした。さらに、P. gingivalisが歯肉組織深部へ移動する一連の動きと周辺組織との相互作用を把握することで、歯周病のみならず、P. gingivalisの関与が示唆される疾患の研究基盤確立への一助としたい。

Outline of Final Research Achievements

Porphyromonas gingivalis is one of the most virulent periodontal disease-causing bacteria, and also involved in various systemic disease such as atherosclerosis and Alzheimer's disease. However, the infection mechanism of periodontal bacteria that leads to disease prevention and treatment has not yet been elucidated. In this study, we prepared a three-dimensional (3D) gingival tissue model infected with periodontal pathogens, and clarified the mechanism by which periodontal pathogens penetrate the barrier of gingival epithelial cell layer. Furthermore, this infection model enabled us to analyze the dynamics of periodontal pathogens within the gingival tissue model and to visualize their invasion into blood capillaries.

Academic Significance and Societal Importance of the Research Achievements

歯周病菌の増殖や感染メカニズムの研究は、歯肉組織を構成する細胞を二次元培養した状態で行われてきた。しかし、硬い平面のディッシュ上で培養された細胞は、実際の生体の状態を反映しておらず、歯周病菌が歯肉組織の深部まで侵入するメカニズムを理解し、対処方法を導き出すことはできない。より生体に近い組成や硬さを有する 3D 歯肉モデルを構築し、歯周病菌を感染させ、そのメカニズム及び深部での動態が解明できれば、歯周病治療に新たな治療標的を提供するだけでなく、歯周病菌が関与する種々の疾患に対する医療へつながる知見が得られると考えた。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Surface pre-reacted glass-ionomer eluate protects gingival epithelium from penetration by lipopolysaccharides and peptidoglycans via transcription factor EB pathway2022

    • Author(s)
      Takeuchi Hiroki、Kato Yuta、Sasaki Naoko、Tanigaki Keita、Yamaga Shunsuke、Mita Ena、Kuboniwa Masae、Matsusaki Michiya、Amano Atsuo
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 7 Pages: e0271192-e0271192

    • DOI

      10.1371/journal.pone.0271192

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Extracellular Matrix Density and Cell Number on Blood Capillary Formation in Three-Dimensional Tissue2022

    • Author(s)
      Shang Yucheng、Zeng Jinfeng、Xie Zhengtian、Sasaki Naoko、Matsusaki Michiya
    • Journal Title

      Bulletin of the Chemical Society of Japan

      Volume: 95 Issue: 8 Pages: 1163-1168

    • DOI

      10.1246/bcsj.20220108

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic analysis of Porphyromonas gingivalis invasion into blood capillaries during the infection process in host tissues using a vascularized three-dimensional human gingival model2021

    • Author(s)
      Sasaki Naoko、Takeuchi Hiroki、Kitano Shiro、Irie Shinji、Amano Atsuo、Matsusaki Michiya
    • Journal Title

      Biomaterials Science

      Volume: 9 Issue: 19 Pages: 6574-6583

    • DOI

      10.1039/d1bm00831e

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of coxsackievirus and adenovirus receptor2021

    • Author(s)
      Takeuchi Hiroki、Yamaga Shunsuke、Sasaki Naoko、Kuboniwa Masae、Matsusaki Michiya、Amano Atsuo
    • Journal Title

      Cellular Microbiology

      Volume: 23 Issue: 11 Pages: 1-13

    • DOI

      10.1111/cmi.13388

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Construction of Vascularized Gingival Tissue as a Model of Porphyromonas gingivalis Infection2020

    • Author(s)
      Naoko Sasaki, Hiroki Takeuchi, Shiro Kitano, Shinji Irie, Atsuo Amano, Michiya Matsusaki
    • Organizer
      World Biomaterials Congress 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 毛細血管網を有する歯肉組織モデルへの感染過程における歯周病菌の動態解析2020

    • Author(s)
      佐々木尚子、竹内洋輝、北野史朗、入江新司、天野敦雄、松崎典弥
    • Organizer
      日本バイオマテリアル学会関西ブロック 第15回若手研究発表会
    • Related Report
      2020 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞構造体及びその製造方法2020

    • Inventor(s)
      松崎典弥、佐々木尚子、天野敦雄、竹内洋輝、北野史朗、入江新司
    • Industrial Property Rights Holder
      大阪大学、凸版印刷
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2019-168577
    • Filing Date
      2020
    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] 細胞構造体及びその製造方法2020

    • Inventor(s)
      松﨑典弥、佐々木尚子、天野敦雄、竹内洋輝、北野史朗、入江新司
    • Industrial Property Rights Holder
      大阪大学、凸版印刷
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Research-status Report
    • Overseas

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Published: 2020-04-28   Modified: 2024-01-30  

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