Involvement of glucose regulated protein 78 in the enamel formation of mouse tooth development

Research Project

Project/Area Number	16K11448
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Morphological basic dentistry
Research Institution	Kyushu University
Principal Investigator	Nagata Kengo 九州大学, 歯学研究院, 助教 (90189134)
Co-Investigator(Kenkyū-buntansha)	清島保九州大学, 歯学研究院, 教授 (20264054) 和田裕子九州大学, 歯学研究院, 助教 (70380706) 藤井慎介九州大学, 歯学研究院, 助教 (60452786)
Project Period (FY)	2016-04-01 – 2020-03-31
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000) Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	歯の発生 / エナメル芽細胞 / エナメル質分泌 / GRP78 / エナメル質形成 / β-カテニン / 石灰化 / 分子シャペロン
Outline of Final Research Achievements	Glucose regulated protein 78 (GRP78) is known to maintain ER environment and promote cell survival against the ER stress. However, it is not well understood the role of GRP78 during enamel formation. To clarify the role of GRP78 on the mineralization of odontogenic epithelium, we examined the immunoexpression of GRP78 in the mouse molar and incisor tooth germs during tooth development. Enamel organ was negative for GRP78 on embryonic day 15 and day 17. Ameloblasts of molar tooth germ on postnatal days 1 and 5 were intensely positive for GRP78. Hertwig's epithelial root sheath was negative for GRP78. Odontogenic epithelium of molar tooth on postnatal day 15 was negative for GRP78. On the other hand, ameloblasts and preameloblasts of the incisor tooth on postnatal day 15 were also intensely positive for GRP78. In conclusion, an involvement of GRP78 in enamel formation is suggested, because of the intense expression of GRP78 is observed in the secretory ameloblasts.
Academic Significance and Societal Importance of the Research Achievements	発生における器官の形態形成の多くは上皮と間葉の相互作用で進んでいく。歯の形態形成は、細胞の分化段階が細かく観察でき、器官形成のモデルとして優れている。これまでに上皮組織や間葉組織に作用する因子が数多く調べられているが、エナメル質形成に関してのGRPの関与は報告されていない。今回、歯の発生機構を明らかにすることで、生物学的な意義だけでなく、再生医療を見据えた臨床応用にむけての意義が考えられる。