Establishment of a novel therapeutic approach for bone diseases.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26713010
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: Nishikawa Keizo 大阪大学, 免疫学フロンティア研究センター, 特任准教授(常勤) (30516290)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 破骨細胞 / エピジェネティクス / 骨芽細胞 / DNAメチル基転移酵素 / Dnmt3a

Outline of Final Research Achievements

Our study revealed that Dnmt3a-mediated DNA methylation regulates osteoclastogenesis via epigenetic repression of the anti-osteoclastogenic gene and that Dnmt3a-deficient osteoclast precursor cells do not undergo osteoclast differentiation efficiently. The importance of Dnmt3a in bone homeostasis was underscored by the observation that mice with an osteoblast/osteoclast-specific deficiency in Dnmt3a exhibit a high bone mass phenotype due to a smaller number of osteoclasts. Furthermore, inhibition of DNA methylation by TF-3 abrogated bone loss in models of osteoporosis, rheumatoid arthritis and cholesteatoma. Thus, our study reveals the role of epigenetic processes involved in bone homeostasis, which may provide a novel therapeutic approach for bone diseases.

Free Research Field

生化学