Elucidation of the mechanism leading to abnormal teeth and craniosynostosis by administration of cyclophosphamide

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K24091
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0907:Oral science and related fields
• Research Institution: Osaka University
• Principal Investigator: Nakatsugawa Kohei 大阪大学, 歯学部附属病院, 医員 (40848248)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 小児がん治療 / 化学療法 / 放射線療法 / シクロホスファミド

Outline of Final Research Achievements

It is known that when cyclophosphamide (CPA), which is a typical anticancer drug, is administered to mice, abnormal tooth of the third molar (M3) occurs depending on the dental stage. In this study, we focused on the Wnt signal, which plays an important role in tooth germ formation, and investigated the effect on the tooth development process by administering CPA using mice that visualize the Wnt signal with fluorescent proteins. As a result, it was suggested that the Wnt signal plays an important role in various sites depending on the stage of tooth formation, and that cell death occurs specifically in the cells around the Wnt signal immediately after CPA administration.

Free Research Field

矯正歯科学

Academic Significance and Societal Importance of the Research Achievements

小児がん治療により顎顔面領域の晩期合併症として顎顔面形態異常や歯の形成異常が生じたという報告が増加している。しかし，小児がん治療が顎顔面領域の発生過程に与える影響については未だ不明な点が多く，更に詳細な研究が必要である。本研究では，顎顔面領域での発生に重要とされているシグナルを蛍光タンパクで可視化するマウスを用い，小児がん治療に用いられる代表的な抗がん剤をこのマウスに投与することで，顎顔面発生ならびに歯の発生過程への影響の探索を行った。本研究結果により，小児がん治療に伴う顎顔面領域の合併症に対する基礎的理解が深まり，予防法や治療法の確立に貢献する事が可能となる。