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A study on the mechanisms of induction and differentiation of stem cells during wound healing and regeneration of dentin-pulp complex

Research Project

Project/Area Number 16H05516
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Conservative dentistry
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)
大倉 直人  新潟大学, 医歯学総合病院, 助教 (00547573)
枝並 直樹  新潟大学, 医歯学系, 助教 (80804567)
細矢 明宏  北海道医療大学, 歯学部, 准教授 (70350824)
入江 一元  北海道医療大学, 歯学部, 教授 (70223352)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords歯髄 / 創傷治癒 / 歯髄幹細胞 / 象牙芽細胞 / 修復象牙質 / 歯髄保存療法 / 修復象牙質形成 / glucose transporter / M2マクロファージ / シュワン細胞 / fibrocyte / 組織再生 / ケイ酸カルシウム系セメント / prostaglandin E2 / 歯学 / α-smooth muscle actin / myofibroblast
Outline of Final Research Achievements

This study aimed to elucidate the mechanism of dental pulp wound healing and reparative dentinogenesis. We investigated the cellular events and expression of related factors after direct pulp capping or pulpotomy. The results suggested that α-SMA-positive myofibroblasts are progenitors of odontoblast-like cells and that TGF-β1 and EDA-fibronectin are involved in their differentiation. In addition, bone marrow-derived mesenchymal cells, fibrocytes, appeared transiently in the early stages and M2 phenotype macrophages colocalized with Schwann cells in healthy as well as inflamed pulp. It was suggested that various types of cells are involved in pulp wound healing and repair process.

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できるだけ歯を保存し、咬合機能を維持することが重要である。歯髄はう蝕や修復処置などの様々な外来侵襲に対して修復・再生する能力を有しているが、そのメカニズムに関しては不明の点が多い。本研究は歯髄の創傷治癒・修復過程において様々な細胞、関連因子が密接に関連して進行することを明らかにした。これらを制御することによって、歯髄創傷治癒を促進させる新たな歯髄保存療法の開発への足掛かりとなると期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (41 results)

All 2020 2019 2018 2017 2016

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 6 results,  Acknowledgement Compliant: 1 results) Presentation (30 results) (of which Int'l Joint Research: 8 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Glucose Transporter 2 and 4 Are Involved in Glucose Supply during Pulpal Wound Healing after Pulpotomy with Mineral Trioxide Aggregate in Rat Molars2020

    • Author(s)
      Tohma Aiko、Ohkura Naoto、Yoshiba Kunihiko、Takeuchi Ryosuke、Yoshiba Nagako、Edanami Naoki、Shirakashi Mari、Ibn Belal Razi Saifullah、Ohshima Hayato、Noiri Yuichiro
    • Journal Title

      Journal of Endodontics

      Volume: 46 Issue: 1 Pages: 81-88

    • DOI

      10.1016/j.joen.2019.10.003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemistry and gene expression of GLUT1, RUNX2 and MTOR in reparative dentinogenesis2020

    • Author(s)
      Takeuchi Ryosuke、Ohkura Naoto、Yoshiba Kunihiko、Tohma Aiko、Yoshiba Nagako、Edanami Naoki、Shirakashi Mari、Belal Razi Saifullah Ibn、Ohshima Hayato、Noiri Yuichiro
    • Journal Title

      Oral Diseases

      Volume: 26 Issue: 2 Pages: 341-349

    • DOI

      10.1111/odi.13230

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] M2 Phenotype Macrophages Colocalize with Schwann Cells in Human Dental Pulp2020

    • Author(s)
      Yoshiba N.、Edanami N.、Ohkura N.、Maekawa T.、Takahashi N.、Tohma A.、Izumi K.、Maeda T.、Hosoya A.、Nakamura H.、Tabeta K.、Noiri Y.、Yoshiba K.
    • Journal Title

      Journal of Dental Research

      Volume: 99 Issue: 3 Pages: 329-338

    • DOI

      10.1177/0022034519894957

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of bone marrow-derived fibrocytes in human dental pulp repair2018

    • Author(s)
      Yoshiba N, Edanami N, Tohma A, Takeuchi R, Ohkura N, Hosoya A, Noiri Y, Nakamura H, Yoshiba K.
    • Journal Title

      International Endodontic Journal

      Volume: 51 Issue: 11 Pages: 1187-1195

    • DOI

      10.1111/iej.12940

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Orthodontic forc application upregulated pain-associated prostaglanidn=2/PGI2-receptor/TRPV1 pathway-related gene expression in rat molars2018

    • Author(s)
      Mariko Ohkura, Naoto Ohkura, Nagako Yoshiba, Kunihiko Yoshiba, Hiroko Ida-Yonemochi, Hayato Ohshima, Isao Saito, Takashi Okiji
    • Journal Title

      Odontology

      Volume: 160(1) Issue: 1 Pages: 2-10

    • DOI

      10.1007/s10266-017-0309-2

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of pulpotomy using mineral trioxide aggregate on prostaglandin transporter and receptors in rat molars2017

    • Author(s)
      Ohkura Naoto、Edanami Naoki、Takeuchi Ryosuke、Tohma Aiko、Ohkura Mariko、Yoshiba Nagako、Yoshiba Kunihiko、Ida-Yonemochi Hiroko、Ohshima Hayato、Okiji Takashi、Noiri Yuichiro
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-10

    • DOI

      10.1038/s41598-017-07167-y

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bioactivity and biomineralization ability of calcium silicate-based pulp-capping materials after subcutaneous implantation2017

    • Author(s)
      Hinata G, Yoshiba K, Han L, Edanami N, Yoshiba N, Okiji T
    • Journal Title

      International Endodontic Journal

      Volume: 50 Issue: S2

    • DOI

      10.1111/iej.12802

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of Dental Pulp Myofibroblasts in Rat Molars after Pulpotomy2017

    • Author(s)
      Edanami N, Yoshiba N, Ohkura N, Takeuchi R, Tohma A, Noiri Y, Yoshiba K
    • Journal Title

      Journal of Endodontics

      Volume: 43 Issue: 7 Pages: 1116-1121

    • DOI

      10.1016/j.joen.2017.02.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characterization of dental pulp myofibroblasts in rat molars after pulpotomy2017

    • Author(s)
      Edanami N, Yoshiba N, Ohkura N, Takeuchi R, Tohma A, Noiri Y, Yoshiba K
    • Journal Title

      Journal of Endodontics

      Volume: 印刷中

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] GaAlAs laser-induced pulp mineralization involves dentin matrix protein 1 and osteopontin expression2016

    • Author(s)
      Shigetani Y, Ohkura N, Yoshiba K, Ohshima H, Hosoya A, Yoshiba N, Okiji T
    • Journal Title

      Oral Disease

      Volume: 22 Issue: 5 Pages: 399-405

    • DOI

      10.1111/odi.12461

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Presentation] 歯髄保存療法と歯髄創傷治癒・修復機構2019

    • Author(s)
      吉羽邦彦
    • Organizer
      令和元年度新潟歯学会第1回例会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ラット臼歯歯髄における創傷治癒時のグルタミン輸送担体の解析2019

    • Author(s)
      大倉直人, 吉羽邦彦, 吉羽永子, 枝並直樹, 遠間愛子, 竹内亮祐, 白柏麻里, 野杁由一郎
    • Organizer
      日本歯科保存学会 2019年度春季学術大会(第150回)
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト歯髄においてシュワン細胞はマクロファージをM2型へ転換する2019

    • Author(s)
      吉羽永子, 大倉直人, 前川知樹, 泉 健次, 細矢明宏, 中村浩彰, 前田健康, 野杁由一郎, 吉羽邦彦
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] なぜ Regenerative endodontic procedures は多様な治癒形態を生じさせるのか-ラット根未完成臼歯における免疫組織学的研究-2019

    • Author(s)
      枝並直樹, 白柏麻里, 吉羽邦彦, 大倉直人, 吉羽永子, 遠間愛子, 竹内亮祐, 野杁由一郎
    • Organizer
      日本歯科保存学会 2019年度秋季学術大会(第151回)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 糖尿病モデルラットを用いた修復象牙質形成時におけるマクロファージの挙動と細胞増殖の解析2019

    • Author(s)
      遠間愛子, 大倉直人, 吉羽邦彦, 吉羽永子, 枝並直樹, 白柏麻里, 竹内亮祐, 野杁由一郎
    • Organizer
      日本歯科保存学会 2019年度秋季学術大会(第151回)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of new rat model for studying regenerative endodontic procedures.2019

    • Author(s)
      Edanami N, Shirakashi M, Yoshiba K, Razi SIB, Ohkura N, Yoshiba N, Tohma A, Takeuchi R, Noiri Y.
    • Organizer
      International Niigata-Taiwan Universities Collaborative Dental Research Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Evaluation of pH and Calcium ion release in vitro and assessment of biomineralization activities of different calcium silicate sealers after rat subcutaneous implant.2019

    • Author(s)
      Razi SIB, Edanami N, Yoshiba K, Shirakashi M, Ohkura N, Yoshiba N, Tohma A, Takeuchi R, Hasegawa T, Noiri Y.
    • Organizer
      International Niigata-Taiwan Universities Collaborative Dental Research Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biocompatibility evaluation of calcium silicate-based materials in rat subcutaneous tissue.2018

    • Author(s)
      Yoshiba K, Edanami N, Tohma A, Takeuchi R, Ohkura N, Yoshiba N, Noiri Y.
    • Organizer
      96th General Session of the International Association for Dental Research (IADR)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Bone marrow-derived fibrocytes are involved in human dental pulp repair.2018

    • Author(s)
      Yoshiba N, Yoshiba K, Edanami N, Tohma A, Takeuchi R, Ohkura N, Oda Y, Hosoya A, Noiri Y, Nakamura H.
    • Organizer
      96th General Session of the International Association for Dental Research (IADR)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歯髄創傷モデルラットを用いた修復象牙質形成時におけるGlut1-Runx2 連関の解析2018

    • Author(s)
      竹内亮祐, 大倉直人, 枝並直樹, 遠間愛子, 吉羽永子, 吉羽邦彦, 野杁由一郎
    • Organizer
      平成30年度新潟歯学会第1回例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 歯髄創傷治癒モデルラットを用いたグルコース輸送担体Glut2とGlut4の局在および遺伝子発現の解析2018

    • Author(s)
      遠間愛子, 大倉直人, 枝並直樹, 竹内亮祐, 吉羽永子, 吉羽邦彦, 野杁由一郎
    • Organizer
      平成30年度新潟歯学会第1回例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラット臼歯歯髄における創傷治癒時のアスコルビン酸輸送経路とその機能解析2018

    • Author(s)
      大倉直人, 遠間愛子, 竹内亮祐, 枝並直樹, 吉羽永子, 吉羽邦彦, 野杁由一郎
    • Organizer
      日本歯科保存学会 2018年度秋季学術大会(第149回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 創傷治癒モデルラットを用いたSmad ubiquitination regulatory factor 1 (SMURF1)およびmammalian target of rapamycin (mTOR)の免疫局在と遺伝子発現解析2018

    • Author(s)
      竹内亮祐, 大倉直人, 遠間愛子, 白柏麻里, 枝並直樹, 吉羽永子, 吉羽邦彦, 野杁由一郎
    • Organizer
      日本歯科保存学会 2018年度秋季学術大会(第149回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 糖尿病モデルラットを用いた歯髄創傷治癒過程におけるCD68およびKi-67の発現解析2018

    • Author(s)
      遠間愛子, 大倉直人, 白柏麻里, 竹内亮祐, 枝並直樹, 吉羽永子, 吉羽邦彦, 野杁由一郎
    • Organizer
      日本歯科保存学会 2018年度秋季学術大会(第149回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] ラットにおけるパルプ・リバスクラリゼーション治療実験モデルの開発2018

    • Author(s)
      白柏麻里, 枝並直樹, 吉羽邦彦, 大倉直人, 吉羽永子, 遠間愛子, 竹内亮祐, 野杁由一郎
    • Organizer
      日本歯科保存学会 2018年度秋季学術大会(第149回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Immunolocalization and gene expression analysis of glucose transporter-1 and runt-related transcription factor 2 in rat model during wound healing of dental pulp2017

    • Author(s)
      Takeuchi R, Ohkura N, Edanami N, Tohma A, Yoshiba N, Yoshiba K, Noiri Y
    • Organizer
      International Collaborative Symposium Faculty of Dentistry Niigata University - Schools of Dentistry Taiwanese Universities
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Immunohistochemical and gene-expression analysis of glucose transporter-4 following direct pulp capping with mineral trioxide aggregate in rat molars2017

    • Author(s)
      Tohma A, Ohkura N, Edanami N, Takeuchi R, Yoshiba N, Yoshiba K, Noiri Y
    • Organizer
      International Collaborative Symposium Faculty of Dentistry Niigata University - Schools of Dentistry Taiwanese Universities
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 歯髄創傷治癒過程におけるマクロファージの集積とmyofibroblast様細胞の分化2017

    • Author(s)
      枝並直樹, 吉羽邦彦, 吉羽永子, 大倉直人, 竹内亮祐, 遠間愛子, 野杁由一郎
    • Organizer
      日本歯科保存学会 2017年度秋季学術大会(第147回)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 歯髄創傷治癒モデルラットを用いたGlucose Transporter-1およびrunt-related transcription factor 2の局在と遺伝子発現解析2017

    • Author(s)
      竹内亮祐, 大倉直人, 枝並直樹, 遠間愛子, 吉羽永子, 吉羽邦彦, 野杁由一郎
    • Organizer
      日本歯科保存学会 2017年度秋季学術大会(第147回)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 歯髄創傷治癒モデルラットを用いたGlucose Transporter-4の局在および遺伝子発現の解析2017

    • Author(s)
      遠間愛子, 大倉直人, 枝並直樹, 竹内亮祐, 吉羽永子, 吉羽邦彦, 野杁由一郎
    • Organizer
      日本歯科保存学会 2017年度秋季学術大会(第147回)
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト歯髄組織創傷治癒過程における骨髄由来間葉系前駆細胞fibrocyteの動態検索2017

    • Author(s)
      吉羽永子, 大倉直人, 細矢明宏, 中村浩彰, 野杁由一郎, 吉羽邦彦
    • Organizer
      第59回歯科基礎医学会学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ラット臼歯断髄後におけるmyofibroblastの動態解析2017

    • Author(s)
      枝並直樹, 吉羽永子, 大倉直人, 野杁由一郎, 吉羽邦彦
    • Organizer
      第50回新潟歯学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 象牙芽細胞分化におけるポリコーム群タンパク質Bmi1の機能2016

    • Author(s)
      細矢明宏,吉羽邦彦,吉羽永子,鷲尾絢子,諸冨孝彦,北村知昭,山本昭夫,中村浩彰
    • Organizer
      日本歯科保存学会 2016年度秋季学術大会(第145回)
    • Place of Presentation
      キッセイ文化ホール(長野県松本市)
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 各種ケイ酸カルシウム系セメントの生体機能性と直接覆髄後の歯髄反応2016

    • Author(s)
      吉羽邦彦,枝並直樹,日向 剛,韓 臨麟,竹内亮祐,遠間愛子,大倉直人,武井絵梨花,吉羽永子,興地隆史
    • Organizer
      第23回日本歯科医学会総会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 培養ヒト歯髄に対するprostaglandin EP4レセプターアゴニストの影響2016

    • Author(s)
      大倉直人,吉羽永子,吉羽邦彦,小田陽平,興地隆史
    • Organizer
      第23回日本歯科医学会総会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Fibrillin-1 microfibrils influence human dental pulp regeneration2016

    • Author(s)
      Yoshiba N, Yoshiba K, Ohkura N, Edanami N, Takeuchi R, Tohma A, Oda Y, Hosoya A, Nakamura H, Okiji T
    • Organizer
      IADR Pulp Biology and Regeneration Group (PBRG) Symposium
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2016-06-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Myofibroblasts in dental pulp healing after pulpotomy with mineral trioxide aggregate (MTA) in rat molars2016

    • Author(s)
      Edanami N, Yoshiba N, Ohkura N, Takeuchi R, Tohma A, Yoshiba K
    • Organizer
      IADR Pulp Biology and Regeneration Group (PBRG) Symposium
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2016-06-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラット臼歯におけるMTAによる直接覆髄後の Glucose Transporter-2の免疫組織化学および遺伝子発現の解析2016

    • Author(s)
      遠間愛子,大倉直人,枝並直樹,竹内亮祐,吉羽永子,吉羽邦彦
    • Organizer
      日本歯科保存学会 2016年度春季学術大会(第144回)
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] ラット臼歯における Mineral trioxide aggregateによる直接覆髄後の Glucose Transporter-1の免疫局在および遺伝子発現解析2016

    • Author(s)
      竹内亮祐,大倉直人,枝並直樹,遠間愛子,吉羽永子,吉羽邦彦
    • Organizer
      日本歯科保存学会 2016年度春季学術大会(第144回)
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] 培養ヒト歯髄に対する prostaglandin EP2 レセプターアゴニストの影響2016

    • Author(s)
      大倉直人,枝並直樹,竹内亮祐,遠間愛子,吉羽永子,吉羽邦彦,小田陽平,興地隆史
    • Organizer
      日本歯科保存学会 2016年度春季学術大会(第144回)
    • Place of Presentation
      栃木県総合文化センター(栃木県宇都宮市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Annual Research Report
  • [Book] MTA その基礎と臨床: 生体材料としての現状と展望2016

    • Author(s)
      吉羽邦彦(分担執筆)
    • Total Pages
      79
    • Publisher
      ヒョーロン・パブリッシャーズ
    • Related Report
      2016 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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