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Establishment of a novel periodontal tissue regeneration therapy using IGF signaling mediated by lncRNA expressed in the dental follicle

Research Project

Project/Area Number 22K17042
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionKyushu University

Principal Investigator

Mitarai Hiromi  九州大学, 大学病院, 助教 (60801660)

Project Period (FY) 2022-04-01 – 2025-03-31
Project Status Completed (Fiscal Year 2024)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2024: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
KeywordsIGFBP3 / 歯根膜組織 / 歯根膜幹細胞 / ヒト歯根膜幹細胞 / 歯根膜 / IGF / 歯周組織再生 / lncRNA
Outline of Research at the Start

歯根膜細胞から、多分化能を有する歯根膜幹細胞へ効率的に誘導し、組織再生療法へ応用する方法を樹立するため、本研究では、歯根膜幹細胞の幹細胞特性に重要な因子を、歯根膜幹細胞を多く含む歯小嚢から探る予定である。我々の微量RNAシークエンス解析結果から歯小嚢に発現が高いことを明らかにしたIGF関連因子とlncRNA H19に着目し、in vivo、in vitroの両面から機能解析を行う。歯根膜幹細胞特性への関連も検討することで、IGF関連因子とH19による幹細胞特性の制御機構を明らかにし、より効率的に歯根膜幹細胞を誘導できる歯周組織再生療法を樹立する。

Outline of Final Research Achievements

Dental follicle, which is part of the tooth germ, differentiates into fibrous periodontal ligament tissue (part of periodontal tissue) that connects the tooth root to the alveolar bone. In order to establish a more effective periodontal tissue regeneration therapy by analyzing the functions of factors strongly expressed in the dental follicle, we focused on the IGFBP3, one of the IGFBP family. We revealed that IGFBP3 promoted collagen production and inhibited mineralization induction of human periodontal ligament stem cell. We also revealed that IGF-related lncRNA H19 inhibited mineralization induction. Furthermore, from organ culture of tooth germ, qRT-PCR revealed that IGFBP3 involved in tooth germ development regulating important gene expression. From these results, it was suggested that IGF-related genes are involved in both tooth germ development and stem cell characteristic, and these might contribute to establish new periodontal regeneration therapy.

Academic Significance and Societal Importance of the Research Achievements

我々のQOL維持のために、歯ならびに歯周組織が維持されることは非常に重要である。そのため、歯や歯周組織の恒常性維持メカニズムの解明、効率的な再生療法の開発は必要不可欠である。本研究により、歯根膜幹細胞の幹細胞能にIGF関連因子が関与していることを明らかにしたことにより、新規性の高い歯周組織再生療法樹立の一助になると思われる。また、歯胚発生への関与を明らかにしたことにより、歯胚発生の詳細なメカニズムの解明に繋がる可能性があると考えられる。

Report

(4 results)
  • 2024 Annual Research Report   Final Research Report ( PDF )
  • 2023 Research-status Report
  • 2022 Research-status Report
  • Research Products

    (6 results)

All 2024 2023 2022

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results)

  • [Journal Article] In vitro evaluation of the antimicrobial properties of terpinen-4-ol on apical periodontitis-associated bacteria2024

    • Author(s)
      Kamiya Harunobu、Haraguchi Akira、Mitarai Hiromi、Yuda Asuka、Wada Hiroko、Shuxin Wang、Ziqing Ran、Weihao Sun、Wada Naohisa
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 30 Issue: 4 Pages: 306-314

    • DOI

      10.1016/j.jiac.2023.10.021

    • Related Report
      2024 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Actin alpha 2, smooth muscle, a transforming growth factor-β1-induced factor, regulates collagen production in human periodontal ligament cells via Smad2/3 pathway2023

    • Author(s)
      Naati Fakatava, Hiromi Mitarai, Asuka Yuda, Akira Haraguchi, Hiroko Wada, Daigaku Hasegawa, Hidefumi Maeda, Naohisa Wada
    • Journal Title

      Journal of Dental Sciences

      Volume: 2 Issue: 2 Pages: 567-576

    • DOI

      10.1016/j.jds.2022.08.030

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] IGFBP3は歯胚発生と歯周組織のリモデリングに関与する2024

    • Author(s)
      王恕心、御手洗裕美、冉子晴、祐田明香、原口晃、孫偉浩、前田英史、和田尚久
    • Organizer
      日本歯科保存学会2023年度秋季学術大会(第159回)
    • Related Report
      2023 Research-status Report
  • [Presentation] スーパーMTAペーストはヒト前骨芽細胞の石灰化誘導能を促進する2024

    • Author(s)
      王恕心、御手洗裕美、Naati Fakatava、王恕心、冉子晴、祐田明香、原口晃、孫偉浩、和田尚久
    • Organizer
      日本歯科保存学会2023年度春季学術大会(第158回)
    • Related Report
      2023 Research-status Report
  • [Presentation] スーパーMTAペーストはヒト前骨芽細胞の石灰化誘導能を促進する2023

    • Author(s)
      御手洗裕美、Fakatava Naati、王恕心、冉子晴、祐田明香、原口晃、孫偉浩、和田尚久
    • Organizer
      日本歯科保存学会
    • Related Report
      2022 Research-status Report
  • [Presentation] ACTA2 regulates human PDL function via interaction with or without TGF-β12022

    • Author(s)
      Naati Fakatava, 御手洗裕美, 祐田明香, 原口晃、長谷川大学、前田英史、和田尚久
    • Organizer
      日本歯科保存学会
    • Related Report
      2022 Research-status Report

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Published: 2022-04-19   Modified: 2026-01-16  

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