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Dental clinical application fo induction odontoblastic differentiation mechanism in Dental Pulp Stem Cells

Research Project

Project/Area Number 20K09947
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionAsahi University

Principal Investigator

Umemura Naoki  朝日大学, 歯学部, 講師 (80609107)

Co-Investigator(Kenkyū-buntansha) 大越 絵実加  青森大学, 薬学部, 教授 (10287667)
近藤 信夫  朝日大学, 歯学部, 教授 (40202072)
高山 英次  朝日大学, 歯学部, 准教授 (70533446)
河野 哲  朝日大学, 歯学部, 教授 (80340074)
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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords歯髄幹細胞 / 象牙芽細胞
Outline of Research at the Start

申請者らは、これまでに歯髄幹細胞の象牙芽細胞への分化誘導メカニズムの解明に取り組んできた結果、CD44-Akt-mTORのシグナルが関与していることが示唆された。そこで、本研究課題では、そのシグナルが象牙芽細胞への分化誘導に重要であるかの検証を行い、さらに歯髄幹細胞を効率的に象牙芽細胞へ分化誘導する新規化合物を検索し、歯髄保護作用と象牙質再生能を動物実験で検証する。これにより歯科臨床応用へのエビデンス構築の分子基盤を得る。本研究により、歯科医療に直結する歯髄保護法、象牙質再生法を提示することが可能となることが期待できる。

Outline of Final Research Achievements

We focused on naphthoquinone derivatives, which are the basic skeleton of vitamin K, as a compound that differentiates dental pulp stem cells into odontoblast-like cells. As a result of screening mainly naphthoquinone derivatives, it was clarified that shikonin retains the function of inducing the differentiation of dental pulp stem cells into odontoblasts. Furthermore, we verified the mechanism by which shikonin induces the differentiation of dental pulp stem cells into odontoblasts. As a result, we clarified that the presence of CD44 induces differentiation through intracellular signal transduction of Akt-mTOR. The results of this research have been published in the scientific journal connective tissue research.

Academic Significance and Societal Importance of the Research Achievements

古くから歯の中に含まれる未分化な細胞群が存在していることが知られていたが、近年の研究で、それらは「歯髄幹細胞」であり、多分化能を保持していることが知られるようなり、骨の再生や神経の再生治療への応用が試みられている。その一方で、歯の再生に向けて歯髄幹細胞の応用研究は少ない。
そこで、本研究課題において、歯髄幹細胞を象牙芽細胞へ分化誘導するメカニズムを探究し、ビタミンKの基本骨格であるナフトキノン誘導体が歯髄幹細胞を象牙芽細胞へと分化誘導することを明らかにし、そのメカニズムも明らかにした。この発見により、歯科臨床応用への期待が高まった。

Report

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

    (4 results)

All 2022 2021 2020

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] ABCG2, CD44 and SOX9 are increased with the acquisition of drug resistance and involved in cancer stem cell activities in head and neck squamous cell carcinoma cells2022

    • Author(s)
      Murakami Koichi、Umemura Naoki、Adachi Makoto、Motoki Masahiro、Ohkoshi Emika
    • Journal Title

      Experimental and Therapeutic Medicine

      Volume: 24 Issue: 6 Pages: 722-722

    • DOI

      10.3892/etm.2022.11658

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Shikonin induces odontoblastic differentiation of dental pulp stem cells via AKT-mTOR-signaling in the presence of CD442021

    • Author(s)
      Kunihiro Kajiura, Naoki Umemura, Emika Ohkoshi, Takahisa Ohta, Nobuo Kondoh, Satoshi Kawano
    • Journal Title

      Connective Tissue Research

      Volume: Jan 12 Issue: 6 Pages: 1-9

    • DOI

      10.1080/03008207.2020.1865937

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metabolomic profiling of tumor-infiltrating macrophages during tumor growth2020

    • Author(s)
      Naoki Umemura, Masahiro Sugimoto, Yusuke Kitoh, Masanao Saio, Hiroshi Sakagami
    • Journal Title

      Cancer immunology, immunotherapy

      Volume: Nor 69(11) Issue: 11 Pages: 2357-2369

    • DOI

      10.1007/s00262-020-02622-8

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Shikonin induces odontoblastic differentiation of dental pulp stem cells via AKT-mTOR-signaling in the presence of CD442020

    • Author(s)
      Kunihiro Kajiura, Naoki Umemura, Kyohei Ueno, Harumi Kawaki, Eiji Takayama, Satoshi Kawano, Nobuo Kondoh
    • Organizer
      歯科基礎医学会学術大会
    • Related Report
      2020 Research-status Report

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

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