Induction of cell differentiation using a-hydroxybutyrate and metabolites

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K09642
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Ohu University
• Principal Investigator: MAEDA TOYONOBU 奥羽大学, 歯学部, 教授 (10382756)
• Co-Investigator(Kenkyū-buntansha): 岡田 英俊 奥羽大学, 歯学部, 教授 (40275623) ; 加藤 靖正 奥羽大学, 歯学部, 教授 (50214408) ; 阿部 匡聡 奥羽大学, 歯学部, 講師 (10254872)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: GPR81 / α-ヒドロキシ酪酸 / 細胞分化

Outline of Final Research Achievements

Addition of α-hydroxybutyrate to the culture medium strongly induced differentiation of stem cells into cells exhibiting osteoblast-like phenotypes in mesenchymal cell cultures. This differentiation induction was also observed when lactate or propionate, which are GPR81 ligands, were added to the culture media. To confirm this stimulation pathway, α-hydroxybutyrate was added to cells transfected with GRP81 shRNA, and the differentiation induction response disappeared. Considering the possibility that a reaction mediated by monocarboxylate transporter was occurring, MCT-1 was forced to be expressed, but there was no change in the differentiation induction. Contrary to expectations, GPR81 ligand strongly promoted differentiation of adipose precursor cells and significantly increased lipid droplet accumulation. It was found that GPR81 ligand may play a role as an accelerator of differentiation rather than acting directly as a reprogramming factor.

Free Research Field

口腔生化学

Academic Significance and Societal Importance of the Research Achievements

近年の組織工学技術の進歩により、in vitroで生体組織を構築し、それを体内に移植する治療が可能になりつつある。しかし、骨組織の再生はその石灰化が必要であるため、軟組織の再生よりも時間がかかる。短時間で骨芽細胞が石灰化するように誘導させる技術の開発は、非常に重要な問題である。本研究ではα-ヒドロキシ酪酸や乳酸、その他のGPR81リガンドが、GPCR81を直接刺激して、間葉系細胞の分化アクセレーターとして、機能していることを突き止めた。これらの知見は、将来の細胞工学において、有意義なものとなると考える。