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The study of tissue engineering utilizing periodontal ligament stem cell induced by tropic factors

Research Project

Project/Area Number 15H05023
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Conservative dentistry
Research InstitutionKyushu University

Principal Investigator

Wada Naohisa  九州大学, 大学病院, 教授 (60380466)

Co-Investigator(Kenkyū-buntansha) 前田 英史  九州大学, 歯学研究院, 教授 (10284514)
清島 保  九州大学, 歯学研究院, 教授 (20264054)
友清 淳  九州大学, 大学病院, 講師 (20507777)
和田 裕子  九州大学, 歯学研究院, 助教 (70380706)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Fiscal Year 2015: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords口腔組織再生 / 幹細胞 / 再生医療 / 歯の発生 / 再生医学 / 歯内疾患
Outline of Final Research Achievements

In this study, Wnt/β-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/β-catenin signaling may associate with odontoma formation. Additionally, we demonstrated the expression patterns and functions of several factors in periodontal ligament and dental pulp tissues, and established parts of mesenchymal stem cell differentiation methods. These results may lead to establish the comprehensive methodology of dental tissue regeneration by the proposal of parts of the mechanisms by which dental mesenchymal stem cells behave.

Academic Significance and Societal Importance of the Research Achievements

複雑な構造物である歯および歯周組織の再生治療には多面的な治療戦略が必要と考えられる。段階的、多角的に検証を行った本研究から得られたsemaphorin3Aや他因子の機能解析結果は、幹細胞研究や再生研究を展開するにあたって有益な情報を提供するもので、さらに将来の組織再生に基づいた新規包括的歯内疾患治療法の技術開発に繋げていくことができると期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (37 results)

All 2019 2018 2017 2016 2015

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 7 results,  Acknowledgement Compliant: 4 results) Presentation (22 results) (of which Int'l Joint Research: 6 results) Book (2 results)

  • [Journal Article] Wnt/β-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development2019

    • Author(s)
      Fujii Shinsuke、Nagata Kengo、Matsumoto Shinji、Kohashi Ken-ichi、Kikuchi Akira、Oda Yoshinao、Kiyoshima Tamotsu、Wada Naohisa
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 4257-4257

    • DOI

      10.1038/s41598-019-39686-1

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 骨組織上に播種した歯髄幹細胞は歯根膜関連遺伝子を発現する-接触する基質の硬さが細胞分化に及ぼす影響-2018

    • Author(s)
      吉田晋一郎, 和田尚久, 長谷川大学, 御手洗裕美, 有馬麻衣, 友清淳, 濱野さゆり, 杉井英樹, 前田英史
    • Journal Title

      日本歯科保存学雑誌

      Volume: 61 Pages: 343-353

    • NAID

      130007543163

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] R-spondin 2 promotes osteoblastic differentiation of immature human periodontal ligament cells through the Wnt/β-catenin signaling pathway2018

    • Author(s)
      Arima Mai、Hasegawa Daigaku、Yoshida Shinichiro、Mitarai Hiromi、Tomokiyo Atsushi、Hamano Sayuri、Sugii Hideki、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Journal of Periodontal Research

      Volume: 54 Issue: 2 Pages: 143-153

    • DOI

      10.1111/jre.12611

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Senescence and odontoblastic differentiation of dental pulp cells2018

    • Author(s)
      Nozu Aoi、Hamano Sayuri、Tomokiyo Atsushi、Hasegawa Daigaku、Sugii Hideki、Yoshida Shinichiro、Mitarai Hiromi、Taniguchi Shuntaro、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Journal of Cellular Physiology

      Volume: 234 Issue: 1 Pages: 849-859

    • DOI

      10.1002/jcp.26905

    • NAID

      120006706625

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extracellular Matrix from Periodontal Ligament Cells Could Induce the Differentiation of Induced Pluripotent Stem Cells to Periodontal Ligament Stem Cell-Like Cells2018

    • Author(s)
      Hamano Sayuri、Tomokiyo Atsushi、Hasegawa Daigaku、Yoshida Shinichiro、Sugii Hideki、Mitarai Hiromi、Fujino Shoko、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Stem Cells and Development

      Volume: 27 Issue: 2 Pages: 100-111

    • DOI

      10.1089/scd.2017.0077

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Wnt5a suppresses osteoblastic differentiation of human periodontal ligament stem cell-like cells via Ror2/JNK signaling2017

    • Author(s)
      Hasegawa Daigaku、Wada Naohisa、Yoshida Shinichiro、Mitarai Hiromi、Arima Mai、Tomokiyo Atsushi、Hamano Sayuri、Sugii Hideki、Maeda Hidefumi
    • Journal Title

      Journal of Cellular Physiology

      Volume: 233 Issue: 2 Pages: 1752-1762

    • DOI

      10.1002/jcp.26086

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Transgelin mediates transforming growth factor-β1-induced proliferation of human periodontal ligament cells2017

    • Author(s)
      Mitarai H.、Wada N.、Hasegawa D.、Yoshida S.、Sonoda M.、Tomokiyo A.、Hamano S.、Serita S.、Mizumachi H.、Maeda H.
    • Journal Title

      Journal of Periodontal Research

      Volume: 52 Issue: 6 Pages: 984-993

    • DOI

      10.1111/jre.12466

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calcium-sensing receptor-ERK signaling promotes odontoblastic differentiation of human dental pulp cells2017

    • Author(s)
      Mizumachi Hiroyuki、Yoshida Shinichiro、Tomokiyo Atsushi、Hasegawa Daigaku、Hamano Sayuri、Yuda Asuka、Sugii Hideki、Serita Suguru、Mitarai Hiromi、Koori Katsuaki、Wada Naohisa、Maeda Hidefumi
    • Journal Title

      Bone

      Volume: 101 Pages: 191-201

    • DOI

      10.1016/j.bone.2017.05.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transforming growth factor-β-induced gene product-h3 inhibits odontoblastic differentiation of dental pulp cells.2017

    • Author(s)
      Serita S, Tomokiyo A, Hasegawa D, Hamano S, Sugii H, Yoshida S, Mizumachi H, Mitarai H, Monnouchi S, Wada N, Maeda H.
    • Journal Title

      Arch Oral Biol.

      Volume: 78 Pages: 135-143

    • DOI

      10.1016/j.archoralbio.2017.02.018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Glial cell line-derived neurotrophic factor from human periodontal ligament cells treated with proinflammatory cytokines promotes neurocytic differentiation of PC12 cells.2017

    • Author(s)
      Yoshida S, Yamamoto N, Wada N, Tomokiyo A, Hasegawa D, Hamano S, Mitarai H, Monnouchi S, Yuda A, Maeda H.
    • Journal Title

      J Cell Biochem.

      Volume: 118 Issue: 4 Pages: 699-708

    • DOI

      10.1002/jcb.25662

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Semaphorin 3A Induces Odontoblastic Phenotype in Dental Pulp Stem Cells.2016

    • Author(s)
      Yoshida S, Wada N, Hasegawa D, Miyaji H, Mitarai H, Tomokiyo A, Hamano S, Maeda H.
    • Journal Title

      Journal of Dental Research

      Volume: 95 Issue: 11 Pages: 1282-1290

    • DOI

      10.1177/0022034516653085

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Is there a role for neural crest stem cells in periodontal regeneration?2015

    • Author(s)
      Tomokiyo A, Hynes K, Gronthos S, Wada N, Bartold PM.
    • Journal Title

      Curr Oral Health Rep

      Volume: 2 Issue: 4 Pages: 275-281

    • DOI

      10.1007/s40496-015-0073-8

    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Immunomodulatory properties of PDLSC and relevance to periodontal regeneration.2015

    • Author(s)
      Wada N, Tomokiyo A, Gronthos S, Bartold PM.
    • Journal Title

      Curr Oral Health Rep

      Volume: 2 Issue: 4 Pages: 245-251

    • DOI

      10.1007/s40496-015-0062-y

    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] LGR4が未分化なヒト歯根膜細胞の増殖能、走化性および骨芽細胞様分化に及ぼす影響2018

    • Author(s)
      有馬麻衣、長谷川大学、吉田晋一郎、御手洗裕美、友清淳、濱野さゆり、杉井英樹、和田尚久、前田英史
    • 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] GDNFは未分化なヒト歯根膜細胞のシュワン細胞分化を誘導する2018

    • Author(s)
      糸山知宏、吉田晋一郎、友清淳、長谷川大学、濱野さゆり、杉井英樹、有馬麻衣、野津葵、和田尚久、前田英史
    • 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] 線維芽細胞における仮足形成因子の探索2018

    • Author(s)
      祐田明香、和田尚久
    • 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] ヒト歯髄細胞の象牙芽細胞様分化におよぼすsFRP1の影響について2018

    • Author(s)
      一法師啓太、友清淳、長谷川大学、濱野さゆり、吉田晋一郎、杉井英樹、有馬麻衣、野津葵、和田尚久、前田英史
    • 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] Semaphorin3Aによる修復象牙質形成過程へのSonic hedgehogシグナルの関与2018

    • Author(s)
      吉田晋一郎、糸山知宏、長谷川大学、有馬麻衣、友清淳、濱野さゆり、杉井英樹、野津葵、和田尚久、前田英史
    • 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] Effects of dopamine on odontoblastic differentiation.2018

    • Author(s)
      Fujino S, Hamano S, Tomokiyo A, Hasegawa D, Yoshida S, Sugii H, Washio A, Wada N, Kitamura C, Maeda H
    • Organizer
      The 11th IFEA World Endodontic Congress
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 象牙芽細胞分化に及ぼすドーパミンの影響について2018

    • Author(s)
      藤野翔香、濱野さゆり、友清淳、長谷川大学、吉田晋一郎、杉井英樹、 鷲尾絢子、御手洗裕美、野津葵、有馬麻衣、和田尚久、北村知昭、前田英史
    • Organizer
      第39回日本歯内療法学会学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] R-spondin2 Enhances Osteoblastic Differentiation of Immature Human Periodontal Ligament Cells.2018

    • Author(s)
      Arima M, Hasegawa D, Yoshida S, Mitarai H, Tomokiyo A, Hamano S, Sugii H, Wada N, Maeda H
    • Organizer
      96th General Session & Exhibition of the International Association for Dental Research (IADR)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Odontoblastic differentiation of senescence dental pulp cells treated by TNF-α.2018

    • Author(s)
      Nozu A, Hamano S, Tomokiyo A, Hasegawa D, Sugii H, Yoshida S, Mitarai H, Taniguchi S, Wada N, Maeda H
    • Organizer
      96th General Session & Exhibition of the International Association for Dental Research (IADR)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規幹細胞関連因子MESTがヒト歯根膜細胞の幹細胞転換に及ぼす影響2018

    • Author(s)
      長谷川大学、長谷川佳那、御手洗裕美、有馬麻衣、濱野さゆり、吉田晋一郎、友清淳、杉井英樹、和田尚久、清島保、前田英史
    • Organizer
      日本歯科保存学会2018年度春季学術大会(第148回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Activin Aがヒト歯根膜細胞およびヒト前骨芽細胞の骨芽細胞様分化に及ぼす影響について2018

    • Author(s)
      杉井英樹、友清淳、濱野さゆり、長谷川大学、吉田晋一郎、御手洗裕美、 野津葵、有馬麻衣、糸山知宏、小野太雅、藤野翔香、一法師啓太、和田尚久、 前田英史
    • Organizer
      日本歯科保存学会2018年度春季学術大会(第148回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] 老化したヒト歯髄細胞の象牙芽細胞様分化におよぼすTNF-αの影響について2018

    • Author(s)
      野津葵、濱野さゆり、友清淳、長谷川大学、吉田晋一郎、杉井英樹、 御手洗裕美、一法師啓太、和田尚久、前田英史
    • Organizer
      日本歯科保存学会2018年度春季学術大会(第148回)
    • Related Report
      2018 Annual Research Report
  • [Presentation] R-spondin2 enhances osteogenesis of immature human periodontal ligament cells through the canonical Wnt signaling pathway2018

    • Author(s)
      Arima M, Hasegawa D, Yoshida S, Mitarai H, Tomokiyo A, Hamano S, Sugii H, Wada N, Maeda H
    • Organizer
      Kyudai Oral Bioscience 2018
    • Related Report
      2017 Annual Research Report
  • [Presentation] Activin A reversely works on the osteoblastic differentiation in human pre-osteoblastic cells and periodontal ligament cells.2017

    • Author(s)
      Sugii H, Tomokiyo A, Hamano S, Hasegawa D, Yoshida S, Mitarai H, Nozu A, Arima M, Itoyama T, Ono T, Fujino S, Ipposhi K, Wada N and Maeda H
    • Organizer
      The 65th Annual Meeting of Japanese Association for Dental Research (JADR)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 歯牙腫におけるWnt/β-cateninシグナルの活性化は軸索伸張制御因子を介して増殖を制御する2017

    • Author(s)
      藤井 慎介、永田 健吾、清島 保、和田 尚久
    • Organizer
      第63回日本病理学会秋期特別総会
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Presentation] R-spondin2はカノニカルWntシグナルを介して未分化なヒト歯根膜細胞の骨芽細胞様分化を促進する2017

    • Author(s)
      有馬麻衣、長谷川大学、吉田晋一郎、御手洗裕美、友清淳、濱野さゆり、杉井英樹、和田尚久、前田英史
    • 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] Tenomodulinがヒト歯根膜細胞の機能維持に及ぼす影響について2017

    • Author(s)
      長谷川大学、和田尚久、有馬麻衣、吉田晋一郎、友清淳、濱野さゆり、御手洗裕美、前田英史
    • Organizer
      第146回日本歯科保存学会春季学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Transgelin Mediates TGF-beta1-induced Human Periodontal Ligament Cell Proliferation2017

    • Author(s)
      Mitarai H, Wada N, Hasegawa D, Yoshida S, Sonoda M, Tomokiyo A, Hamano S, Maeda H
    • Organizer
      95th General Session & Exhibition of the International Association for Dental Research (IADR)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of a novel periodontal ligament stem cell marker.2016

    • Author(s)
      Hasegawa D, Wada N, Hamano S, Tomokiyo A, Yoshida S, Mitarai H, Sonoda M, Sugii H, Maeda H
    • Organizer
      94th General Session & Exhibition of the IADR
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Semaphorin 3A induces odontoblastic phenotype in dental pulp stem cells.2016

    • Author(s)
      Yoshida S, Wada N, Hasegawa D, Tomokiyo A, Hamano S, Mitarai H, Hideki S, Maeda H
    • Organizer
      94th General Session & Exhibition of the IADR
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-06-22
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] MESTはヒト歯根膜幹細胞における幹細胞特性の維持に関与する.2016

    • Author(s)
      長谷川大学、和田尚久、濱野さゆり、友清淳、吉田晋一郎、御手洗裕美、園田麻衣、杉井英樹、前田英史
    • Organizer
      第144回日本歯科保存学会春季学術大会
    • Place of Presentation
      宇都宮市
    • Year and Date
      2016-06-09
    • Related Report
      2015 Annual Research Report
  • [Presentation] R-spondin2が未分化なヒト歯根膜細胞の線維芽細胞様分化に及ぼす影響2016

    • Author(s)
      園田麻衣、長谷川大学、和田尚久、吉田晋一郎、御手洗裕美、友清淳、濱野さゆり、前田英史.
    • Organizer
      第145回日本歯科保存学会秋季学術大会
    • Related Report
      2016 Annual Research Report
  • [Book] Dental Stem Cells2015

    • Author(s)
      Wada N, Tomokiyo A, Maeda H
    • Total Pages
      328
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report
  • [Book] Frontiers in stem cell and regeneration medicine research vol.22015

    • Author(s)
      Tomokiyo A, Wada N, Maeda H
    • Total Pages
      294
    • Publisher
      Bentham Science Publishers
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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