Effect of the hydroxamic acid class of inhibitors on osteoclast differentiation

Research Project

Project/Area Number	18K09928
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57080:Social dentistry-related
Research Institution	Osaka Dental University
Principal Investigator	Ikeo Takashi 大阪歯科大学, 歯学部, 教授 (40159603)
Co-Investigator(Kenkyū-buntansha)	堂前英資大阪歯科大学, 歯学部, 講師 (50454559)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	破骨細胞 / ヒドロキサム酸系阻害剤 / 歯周病 / GM6001 / MMP阻害剤
Outline of Final Research Achievements	We examined the effect of the hydroxamic acid class of metalloprotease inhibitors on osteoclast differentiation. Our results suggest that the hydroxamic acid class inhibitors increased osteoclast differentiation at later periods of the process. Although we did not identify the target of hydroxamic acid class inhibitors, our results suggest that the inhibitors might increase the interaction of osteoclast-precursors to become multi-nucleated giant cells. Our results suggest that metalloproteases seem to control the interaction of osteoclast precursors, and clarifying this process could be a clue to developing strategies for the prevention of pathogenic bone resorption.
Academic Significance and Societal Importance of the Research Achievements	骨粗鬆症や歯周病などの病的骨代謝疾患の治療薬は、歴史があり信頼性のあるものから特定の分子を標的とした抗体薬などが広く用いられている。しかしながら頻度は少ないとはいえ歯科領域で問題となる顎骨壊死などの副反応が解決すべき課題として残されている。従来の治療薬とは異なる標的の同定と、その知見に基づく治療薬の開発が必要である。本研究では、破骨細胞分化を促進する低分子化合物（ヒドロキサム酸系阻害剤）の発見と、そのメカニズムの解析を行い、新たな治療標的の可能性を広げる結果が得られたことから、より安全な治療薬開発への糸口となると考えられる。