Elucidation of the molecular mechanism of the bone matrix protein osteocalcin in protecting brain function

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K09510
• 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: Higashi Sen 九州歯科大学, 歯学部, 助教 (40228705)
• Co-Investigator(Kenkyū-buntansha): 竹内 弘 九州歯科大学, 歯学部, 教授 (70304813)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 神経細胞 / 骨 / オステオカルシン

Outline of Final Research Achievements

The bone protein osteocalcin (OC) improves systemic sugar and energy metabolism via the receptor GPRC6A. On the other hand, it was reported that OC passes through the blood-brain barrier and placenta followed by migrating into the brain, thus maintains cognitive function, exerts antidepressant action, and supports fetal brain development and learning / memory ability based on the experiments using mice. However, the direct action of OC on nerve cells has not been elucidated. In this study, we showed that OC acts directly on neurons via the receptor GPR158, promotes cell proliferation and differentiation, and suppresses oxidative stress-induced apoptotic cell death. This result is expected to contribute to the development of new preventive and therapeutic strategies for cognitive and developmental disorders targeting OC and GPR158.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

骨タンパク質オステオカルシン（OC）による認知機能の維持・抗うつ作用や、胎児の脳の発達と学習・記憶能力の支持する効果が報告されたが、神経細胞に対するOCの直接作用は不明であった。本研究でOCが受容体GPR158を介して神経細胞に直接作用し、脳機能保護につながる様々な効果を発揮することが示された。社会問題となっている認知障害や発達障害に対する新たな予防・治療戦略の開発に寄与することが期待される。