Budget Amount *help |
¥21,450,000 (Direct Cost: ¥16,500,000、Indirect Cost: ¥4,950,000)
Fiscal Year 2016: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
|
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.
|