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A study on the mechanisms of induction and differentiation of Gli1-positive stem cells during wound healing and regeneration of dental pulp

Research Project

Project/Area Number 21K09914
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 InstitutionNiigata University

Principal Investigator

YOSHIBA Kunihiko  新潟大学, 医歯学系, 教授 (30220718)

Co-Investigator(Kenkyū-buntansha) 吉羽 永子  新潟大学, 医歯学総合病院, 講師 (10323974)
枝並 直樹  新潟大学, 医歯学系, 助教 (80804567)
大倉 直人  新潟大学, 医歯学総合病院, 助教 (00547573)
細矢 明宏  北海道医療大学, 歯学部, 教授 (70350824)
入江 一元  北海道医療大学, 歯学部, 教授 (70223352)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords歯髄創傷治癒 / 歯髄保存療法 / 再生歯内療法 / 間葉系幹細胞 / マクロファージ / バイオセラミックス / 歯髄 / 創傷治癒 / バイオセラミック / Gli1陽性細胞 / Gli1 / 象牙芽細胞
Outline of Research at the Start

歯の保存には歯髄の保護・保存が重要であり、生活歯髄保存療法や失われた歯髄に対して再生歯内療法が試みられている。しかし歯髄の創傷治癒・再生過程において中心的役割を果たす間葉系幹細胞の動態と象牙芽細胞への分化誘導機構は未解明である。本研究では、転写因子Gli1発現細胞の動態を細胞系譜解析により検索するとともに、新生象牙芽細胞の分化過程における一連のシグナル分子の発現を解析し、細胞分化誘導因子を同定する。以上より、自己組織に含まれる間葉系幹細胞のホーミングと細胞分化を促進する歯髄/象牙質再生療法・再生歯内療法の開発を目指す。

Outline of Final Research Achievements

The purpose of this study is to elucidate the mechanism of wound healing and regeneration after vital pulp therapy and regenerative endodontic therapy. We observed the changes in the distribution of mesenchymal stem cells and macrophages, and investigated the effect of the bioactivity of pulp capping materials on wound healing. Gli1-positive cells in the molar periodontal ligament were found to have stem cell properties, as they exhibited high colony-forming unit fibroblast (CFU-F) activity and multipotency and induced hard tissue formation. In rats with ascorbic acid deficiency or hyperglycemia, macrophage accumulation continued after pulpotomy, and hard tissue formation was delayed. We also found that the in vivo apatite formation ability of bioceramic-containing materials is related to wound healing in the dental pulp and apical periodontal tissues.

Academic Significance and Societal Importance of the Research Achievements

超高齢社会を迎え、健康長寿社会の実現のために口腔機能の維持、特に歯の保存と咬合機能の維持が益々重要となっている。歯の保存のために歯髄の保護・保存が重要と考えられており、さらに失われた歯髄を再生させる試みもなされている。本研究は歯髄の創傷治癒・再生過程において中心的役割を果たす間葉系幹細胞ならびにマクロファージの動態について検索するとともに、臨床応用する上で重要な覆髄材料の生体機能性について検討したもので、効果的な歯髄保存療法あるいは再生歯内療法の開発へ繋がるものと期待される。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (21 results)

All 2024 2023 2022 2021

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 8 results) Presentation (10 results)

  • [Journal Article] Bioactivity of Calcium Silicate Cements and Pulpal Wound Healing in Vital Pulp Therapy2024

    • Author(s)
      吉羽 邦彦
    • Journal Title

      The Japanese Journal of Conservative Dentistry

      Volume: 67 Issue: 1 Pages: 1-9

    • DOI

      10.11471/shikahozon.67.1

    • ISSN
      0387-2343, 2188-0808
    • Year and Date
      2024-02-29
    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wound-healing Processes After Pulpotomy in the Pulp Tissue of Type 1 Diabetes Mellitus Model Rats2024

    • Author(s)
      Baldeon-Gutierrez Rosa、Ohkura Naoto、Yoshiba Kunihiko、Yoshiba Nagako、Tohma Aiko、Takeuchi Ryosuke、Belal Razi Saifullah Ibn、Edanami Naoki、Takahara Shintaro、Gomez-Kasimoto Susan、Ida Takako、Noiri Yuichiro
    • Journal Title

      Journal of Endodontics

      Volume: 50 Issue: 2 Pages: 196-204

    • DOI

      10.1016/j.joen.2023.10.016

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vivo Assessment of the Apatite-Forming Ability of New-Generation Hydraulic Calcium Silicate Cements Using a Rat Subcutaneous Implantation Model2023

    • Author(s)
      Edanami Naoki、Takenaka Shoji、Ibn Belal Razi Saifullah、Yoshiba Kunihiko、Takahara Shintaro、Yoshiba Nagako、Ohkura Naoto、Noiri Yuichiro
    • Journal Title

      Journal of Functional Biomaterials

      Volume: 14 Issue: 4 Pages: 213-213

    • DOI

      10.3390/jfb14040213

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SVCT2-GLUT1-mediated ascorbic acid transport pathway in rat dental pulp and its effects during wound healing2023

    • Author(s)
      Ohkura Naoto、Yoshiba Kunihiko、Yoshiba Nagako、Edanami Naoki、Ohshima Hayato、Takenaka Shoji、Noiri Yuichiro
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 1251-1251

    • DOI

      10.1038/s41598-023-28197-9

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vivo Assessment of the Calcium Salt-Forming Ability of a New Calcium Silicate-Based Intracanal Medicament: Bio-C Temp2023

    • Author(s)
      Edanami Naoki、Belal Razi Saifullah Ibn、Takenaka Shoji、Yoshiba Kunihiko、Gutierrez Rosa Edith Baldeon、Takahara Shintaro、Yoshiba Nagako、Ohkura Naoto、Noiri Yuichiro
    • Journal Title

      Dentistry Journal

      Volume: 11 Issue: 4 Pages: 91-91

    • DOI

      10.3390/dj11040091

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GaAlAs Diode Laser-induced Mineralized Tissue Formation in Dentin/Pulp Complex: A Review2022

    • Author(s)
      Okiji Takashi、Shigetani Yoshimi、Yoshiba Kunihiko、Ohshima Hayato
    • Journal Title

      The Journal of Japan Society for Laser Surgery and Medicine

      Volume: 43 Issue: 2 Pages: 113-119

    • DOI

      10.2530/jslsm.jslsm-43_0015

    • ISSN
      0288-6200, 1881-1639
    • Year and Date
      2022-07-15
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gli1+-PDL Cells Contribute to Alveolar Bone Homeostasis and Regeneration2022

    • Author(s)
      Shalehin N.、Seki Y.、Takebe H.、Fujii S.、Mizoguchi T.、Nakamura H.、Yoshiba N.、Yoshiba K.、Iijima M.、Shimo T.、Irie K.、Hosoya A.
    • Journal Title

      Journal of Dental Research

      Volume: 101 Issue: 12 Pages: 1537-1543

    • DOI

      10.1177/00220345221106921

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of a resin-modified calcium silicate cement on inflammatory cell infiltration and reparative dentin formation after pulpotomy in rat molars2022

    • Author(s)
      Naoki Edanami, Razi Saifullah Ibn Belal, Kunihiko Yoshiba, Nagako Yoshiba, Naoto Ohkura, Shoji Takenaka, Yuichiro Noiri
    • Journal Title

      Australian Endodontic Journal

      Volume: in press Issue: 2 Pages: 297-304

    • DOI

      10.1111/aej.12568

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Apatite-Forming Ability of Flowable vs. Putty Formulations of Newly Developed Bioactive Glass-Containing Endodontic Cement2021

    • Author(s)
      Edanami Naoki、Ibn Belal Razi Saifullah、Takenaka Shoji、Yoshiba Kunihiko、Yoshiba Nagako、Ohkura Naoto、Takahara Shintaro、Noiri Yuichiro
    • Journal Title

      Applied Sciences

      Volume: 11 Issue: 19 Pages: 8969-8969

    • DOI

      10.3390/app11198969

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of calcium and hydroxyl ion release ability and in vivo apatite-forming ability of three bioceramic-containing root canal sealers2021

    • Author(s)
      Belal Razi Saifullah Ibn、Edanami Naoki、Yoshiba Kunihiko、Yoshiba Nagako、Ohkura Naoto、Takenaka Shoji、Noiri Yuichiro
    • Journal Title

      Clinical Oral Investigations

      Volume: 26 Issue: 2 Pages: 1443-1451

    • DOI

      10.1007/s00784-021-04118-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laminin Isoforms in Human Dental Pulp: Lymphatic Vessels Express Laminin-332, and Schwann Cell?Associated Laminin-211 Modulates CD163 Expression of M2-like Macrophages2021

    • Author(s)
      Yoshiba Nagako、Edanami Naoki、Ohkura Naoto、Maekawa Tomoki、Takahashi Naoki、Tsuzuno Takahiro、Maeda Takeyasu、Tabeta Koichi、Izumi Kenji、Noiri Yuichiro、Yoshiba Kunihiko
    • Journal Title

      ImmunoHorizons

      Volume: 5 Issue: 12 Pages: 1008-1020

    • DOI

      10.4049/immunohorizons.2100110

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Impact of glutamine-transporter during wound-healing in rat pulpotomized model2023

    • Author(s)
      Gomez-Kashimoto S, Ohkura N, Yoshiba K, Yoshiba N, Baldeon-Gutierrez R, Edanami N, Takahara S, Ida T, Takenaka S, Noiri Y
    • Organizer
      The 71st Annual Meeting of JADR
    • Related Report
      2023 Annual Research Report
  • [Presentation] Wound-healing mechanism after pulpotomy in Type 1 and 2 diabetes-mellitus-rats2023

    • Author(s)
      Baldeon-Gutierrez R, Ohkura N, Yoshiba K, Yoshiba N, Edanami N, Takahara S, Gomez-Kashimoto S, Ida T, Takenaka S, Noiri Y
    • Organizer
      The 71st Annual Meeting of JADR
    • Related Report
      2023 Annual Research Report
  • [Presentation] 再生歯内療法後の治癒過程初期における各種間葉系幹細胞マーカー陽性細胞の局在性2023

    • Author(s)
      髙原信太郎,大倉直人,吉羽永子,竹中彰治,枝並直樹,吉羽邦彦,野杁由一郎
    • Organizer
      日本歯科保存学会2023年秋季学術大会(第159回)
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯根形成時におけるTissue nonspecific alkaline phosphatase の機能解析2023

    • Author(s)
      大倉直人,吉羽永子,高原信太郎,Rosa Edith Baldeon-Gutierrez,Susan Gomez-Kashimoto,井田貴子,枝並直樹,竹中彰治,吉羽邦彦,野杁由一郎
    • Organizer
      日本歯科保存学会2023年秋季学術大会(第159回)
    • Related Report
      2023 Annual Research Report
  • [Presentation] 歯髄再生療法モデルラットを用いた歯根成長段階による治癒形態の比較解析2023

    • Author(s)
      髙原信太郎,大倉直人,吉羽邦彦,吉羽永子,竹中彰治,枝並直樹,庭野和明,野杁由一郎
    • Organizer
      日本歯科保存学会2023年春季学術大会(第158回)
    • Related Report
      2023 Annual Research Report
  • [Presentation] 生体活性はケイ酸カルシウム系セメントに普遍的な特性か? -18種のケイ酸カルシウム系セメントの生体内評価-2022

    • Author(s)
      枝並直樹, イブンベラル・ラジサイフラー, 竹中彰治, 吉羽邦彦, 大倉直人, 吉羽永子, 野杁由一郎
    • Organizer
      日本歯科保存学会2022年度春季学術大会(第156回)
    • Related Report
      2022 Research-status Report
  • [Presentation] 歯根形成時におけるピロリン酸および無機リン酸の影響2022

    • Author(s)
      大倉直人, 吉羽邦彦, 枝並直樹, 竹中彰治, 野杁由一郎
    • Organizer
      第43回日本歯内療法学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 根尖孔外に漏出したバイオセラミック系シーラーと歯周組織の相互作用2022

    • Author(s)
      高原信太郎, 枝並直樹, 竹中彰治, 吉羽邦彦, 大倉直人, 吉羽永子, 野杁由一郎
    • Organizer
      日本歯科保存学会2022年度秋季学術大会(第157回),
    • Related Report
      2022 Research-status Report
  • [Presentation] ケイ酸カルシウム系貼薬剤と水酸化カルシウム系貼薬剤のBiomineralization Abilityの比較2022

    • Author(s)
      枝並直樹, 竹中彰治, 吉羽邦彦, 大倉直人, 吉羽永子, 高原信太郎, 野杁由一郎
    • Organizer
      日本歯科保存学会2022年度秋季学術大会(第157回)
    • Related Report
      2022 Research-status Report
  • [Presentation] Apatite forming ability of different endodontic bioceramics in vivo and under in vivo mimicking condition2021

    • Author(s)
      Ibn Belal Razi Saifullah, Edanami Naoki, Yoshiba Kunihiko, Yoshiba Nagako, Ohkura Naoto, Takenaka Shoji, Noiri Yuichiro
    • Organizer
      令和3年度新潟歯学会第1回例会
    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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