2020 Fiscal Year Final Research Report

The mechanism of BMP-3b on regulating myogenesis of skeletal muscle stem cells

Research Project

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Project/Area Number	18K09524
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57010:Oral biological science-related
Research Institution	Kyushu Dental College
Principal Investigator	Kokabu Shoichiro 九州歯科大学, 歯学部, 教授 (30448899)
Co-Investigator(Kenkyū-buntansha)	松原琢磨九州歯科大学, 歯学部, 准教授 (00423137) 日野純国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40260351) 小野悠介熊本大学, 発生医学研究所, 准教授 (60601119) 松尾拡九州歯科大学, 歯学部, 教授 (70238971) 人見涼露日本大学, 歯学部, 助教 (70548924)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	BMP / BMP-3b / GDF10 / サルコペニア / 筋再生
Outline of Final Research Achievements	Real time PCR analysis revealed that BMP-3b mRNA is abundantly expressed in skeletal muscle tissue. Recombinant rat (rr) BMP-3b derived from CHO cells increased CAGA-luciferase activity as well as the expression levels of PAI-1, a Smad2/3 target gene. Treatment of C2C12 cells, or primary cultured satellite cells (SCs) with rrBMP-3b suppressed the expression of myogenic marker genes such as myogenin and myosin heavy chain. Furthermore, treatment of C2C12 cells with SB431542, kinase inhibitor of ALK4, 5 and 7, rescued the suppressive effect of BMP-3b on myogenesis. The expression levels of BMP-3b decreased with myogenesis of SCs. Moreover, rrBMP-3b also suppressed myogenesis in SCs. Treatment of SCs with a neutralizing antibody to BMP-3b also enhanced the myogenesis of SCs. Endogenous BMP-3b expressed by SCs physiologically regulates myogenesis.
Free Research Field	口腔科学
Academic Significance and Societal Importance of the Research Achievements	骨格筋は定常状態でも一定の割合で分解し減少し，骨格筋幹細胞であるサテライト細胞が増殖・分化することで減少した骨格筋量と同量の骨格筋を再生し，骨格筋の恒常性が維持される．サルコペニアなどの骨格筋萎縮性の疾患ではこの分解・減少と再生のバランスが崩れ，骨格筋の分解・減少が相対的に再生を上回ることで生じる．今回われわれはBMP-3bがサテライト細胞の分化を強力に阻害することを突き止めた．それとは逆に，BMP-3bの抗体は筋分化を強力に促進した．今後，BMP-3b抗体投与によりin vivoで加齢に伴う骨格筋量の減少が軽減されることが示せれば、BMP-3bがサルコペニアの予防や治療法の標的になり得る。