Establishment of a novel therapeutic approach for bone diseases.
| Project/Area Number |
26713010
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Partial Multi-year Fund |
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| Research Field |
General pharmacology
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| Research Institution | Osaka University |
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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)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| 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)
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| 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 / エピジェネティック制御 / DNAメチル化 / 真珠腫 / エピゲノム創薬 / 異所性骨化 / マウス / Enpp1 / 転写制御 / iPSC / 細胞分化 / コンディショナルノックアウト |
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| 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.
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Report
(4 results)
Research Products
(44 results)
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[Journal Article] Intercellular communication between keratinocytes and fibroblasts induces local osteoclast differentiation: a mechanism underlying cholesteatoma-induced bone destruction.2016
Author(s)
3.Iwamoto Y, Nishikawa K, Imai R, Furuya M, Uenaka M, Ohta Y, Morihana T, Itoi-Ochi S, Penninger JM, Katayama I, Inohara H and Ishii M
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Journal Title
Molecular and Cellular Biology
Volume: 36
Issue: 11
Pages: 1610-20
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Intercellular communication between keratinocytes and fibroblasts induces local osteoclast differentiation: a mechanism underlying cholesteatoma-induced bone destruction.2016
Author(s)
Iwamoto Y, Nishikawa K, Imai R, Furuya M, Uenaka M, Ohta Y, Morihana T, Itoi-Ochi S, Penninger JM, Katayama I, Inohara H and Ishii M
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Journal Title
Molecular and Cellular Biology
Volume: inpress
Related Report
Peer Reviewed / Acknowledgement Compliant
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