2021 Fiscal Year Final Research Report

Regulatory mechanism of bone development mediated by channel kinase TRPM7

Research Project

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Project/Area Number	19H03822
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 57010:Oral biological science-related
Research Institution	Fukuoka Dental College
Principal Investigator	Okabe Koji 福岡歯科大学, 口腔歯学部, 教授 (80224046)
Co-Investigator(Kenkyū-buntansha)	進正史福岡歯科大学, 口腔歯学部, 講師 (70549261) 鍛治屋浩福岡歯科大学, 口腔歯学部, 講師 (80177378) 岡本富士雄福岡歯科大学, 口腔歯学部, 講師 (60153938) 溝口利英東京歯科大学, 歯学部, 准教授 (90329475) 松下正之琉球大学, 医学(系)研究科(研究院), 教授 (30273965)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	TRPM7 / 骨格形成 / ミネラル輸送 / キナーゼ活性 / 骨髄間葉系細胞
Outline of Final Research Achievements	Channel kinase TRPM7 is a unique bi-functional cation channel containing a protein kinase domain and highly expressed in teeth. Using mesenchymal cell specific TRPM7 conditional knock out (Prx1/cKO) mice and TRPM7 kinase mutant (KR) mice, the function of mineral transport and kinase activity of TRPM7 in bone formation was investigated. TRPM7 expression was mainly observed in growth plate cartilage and trabecular bone. Prx1/cKO mice showed shortened bones and impaired trabecular bone formation, and suppression of the growth plate area due to impaired differentiation of hypertrophic chondrocyte. Moreover, bone resorption markers and RANKL expression tended to be upregulated. No phenotype was observed in KR mice, indicating less involvement in the kinase activity. These findings suggest that TRPM7 is critical as a cation channel rather than as a kinase in bone development via the regulation of both chondrogenesis and osteoclastogenesis.
Free Research Field	口腔生理学
Academic Significance and Societal Importance of the Research Achievements	骨の発達や形成を担うミネラル輸送の分子同定や石灰化機構に関しては多くが不明であり解明すべき必須課題である。本研究の学術的意義は、ミネラル輸送とキナーゼ活性を有するTRPM7に注目し、骨髄間葉系細胞に特異的な遺伝子改変マウスを用いて、骨格形成におけるミネラル輸送分子のシグナル伝達機構や機能との関係、特にin vivo実験系における骨格形成への直接的な機能について取組む点である。これらの取組は、骨格形成異常の病態の理解や骨組織の再生研究へ新しい戦略を提供し、社会的な貢献にもつながると考えられる。