Development of a method for suppressing bone destruction targeting cholesterol acyltransferase.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11993
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Periodontology
• Research Institution: Showa University
• Principal Investigator: Sakai Nobuhiro 昭和大学, 歯学部, 講師 (90286849)
• Co-Investigator(Kenkyū-buntansha): 高見 正道 昭和大学, 歯学部, 教授 (80307058) ; 古賀 貴子 東京大学, 医科学研究所, 特任准教授 (90451905)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脂質代謝 / 骨代謝 / 破骨細胞 / 骨密度

Outline of Final Research Achievements

Antibiotics are mainly used as local therapeutic agents for chronic periodontal disease, but development of therapeutic agents for periodontal disease that promote bone regeneration is expected.
Recently, a selective inhibitor targeting a new molecule of cholesterol acyltransferase (ACAT) isozyme ACAT2 has been created as a novel lipid metabolism improving drug. As a result, ACAT2 inhibitors significantly reduced lipid markers.
In the osteoclast and osteoblast cultures had no effect on differentiation. The effect of increasing bone mass could not be observed in the experimental ovariectomized (OVX) mouse.On the other hand, in the mice fed a high-fat diet for a long period of time, pulp stenosis due to dentin thickness of the incisors was observed.

Free Research Field

歯科薬理学

Academic Significance and Societal Importance of the Research Achievements

新規脂質代謝改善薬としてコレステロールアシル転移酵素（ACAT）のアイソザイム ACAT2を選択的に阻害する薬はスタチンと同程度に脂質代謝を改善できたことから新規脂質代謝改善薬として期待が高まる。これまでに脂質代謝改善であるスタチンには骨形成促進作用が報告され、骨粗鬆症治療薬として期待されたが効果は低かった。ACAT2阻害薬も破骨細胞の分化抑制を示したが動物実験においては骨形成作用は示さなかった。しかし骨代謝には影響を起こさず脂質代謝を改善できる新規薬と認可に向け、開発を進めることが期待される。