Mechanisms maintaining quiescent stem cells by Shh signaling in the apical bud of incisors and developing molars in mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K11730
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Conservative dentistry
• Research Institution: Chiba Prefectural University of Health Sciences (2018-2020); Kyushu University of Nursing and Social Welfare (2017)
• Principal Investigator: Ishikawa Yuko 千葉県立保健医療大学, 健康科学部, 教授 (40401757)
• Co-Investigator(Kenkyū-buntansha): 大島 勇人 新潟大学, 医歯学系, 教授 (70251824) ; 中富 満城 九州歯科大学, 歯学部, 講師 (10571771) ; 斎藤 浩太郎 新潟大学, 医歯学系, 助教 (10733719) ; 依田 浩子 新潟大学, 医歯学系, 准教授 (60293213)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 歯髄 / ソニック・ヘッジホッグシグナル / 静的幹細胞 / Gliタンパク / Ptch1受容体 / マウス / 発生

Outline of Final Research Achievements

In molars, dense H2B-GFP-label-retaining cells (H2B-GFP-LRCs) were densely distributed throughout the dental pulp during P1 to postnatal week 2 (P2W) and decreased in number by postnatal P3W, whereas the number of dense H2B-GFP-LRCs in the subodontoblastic layer increased in number at P2W. Gli1+ and Ptch1+ cells were distributed throughout the enamel organ and dental pulp, including the odontoblast and subodontoblastic layers. In incisors, the apical bud contained H2B-GFP-LRCs, Gli1+ cells, and Ptch1+ cells. The addition of Shh antibody to explants induced a decrease in the number of Sox2+ cells due to the increase in apoptotic cells in the apical bud.
Thus, the Shh-Ptch-Gli signaling pathway plays a role in maintaining quiescent adult stem cells and regulating the function of odontoblasts.

Free Research Field

歯科衛生士教育

Academic Significance and Societal Importance of the Research Achievements

本研究では、ShhレセプターであるPtch1・2の異なる発現パターンに着目し、Shhシグナルと静的幹細胞維持機構との関連を解明したことは、Shhの新たな役割の解明に繋がった。また、マウス切歯および臼歯発生過程における静的幹細胞維持とShhシグナルとの関連を解明したことから、静的幹細胞を用いた歯髄再生療法への展開に貢献できる。