Development of new therapy for osteogenesis imperfecta targeting bone coupling

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K15708
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Osaka University
• Principal Investigator: Ohata Yasuhisa 大阪大学, 大学院医学系研究科, 助教 (20805460)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 骨形成不全症

Outline of Final Research Achievements

Osteogenesis imperfecta (OI) is a congenital bone dysplasia with bone fragility. Previous sudies have suggested that abnormalities in bone coupling accelerated bone resorption by osteoclasts, which exacerbate the OI pathology. The aim of this study was to develop a novel treatment for OI targeting bone coupling abnormalities. We extracted bone marrow from oim mice, an OI model mouse, and performed primary osteoblast culture. Then we comprehensively identified molecules involved in osteoclast differentiation using RNAseq. In this study, we established an experimental system for analyzing bone evaluation in OI model mice and a method for isolating osteoblasts and osteoclasts, and confirmed that osteoclast differentiation is actually enhanced in OI. Finally, we identified candidate molecules that could be responsible for enhanced osteoclast differentiation.

Free Research Field

骨系統疾患

Academic Significance and Societal Importance of the Research Achievements

本研究では骨形成不全症における破骨細胞機能亢進を惹起する候補分子の同定を行った。さらに候補分子を発現する細胞の特徴をシングルセルRNAseqで解析した。これまで骨形成不全症では病態特異的治療法がなく、特に重症患者においては既存の姑息的治療では、十分な効果が乏しく、QOLの改善につながっていないことが問題となっていた。本研究で見いだされた病態をさらに解明し、候補分子発現細胞を標的とした治療法を検討することにより、より骨形成不全症の病態に特異的な治療法の開発が進められることが期待される。