2013 Fiscal Year Final Research Report
The mechanism of transcriptional regulation of Runx2 gene and the program of skeletal development
| Project/Area Number |
22249062
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
KOMORI Toshihisa 長崎大学, 医歯(薬)学総合研究科, 教授 (00252677)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Hideki 長崎大学, 大学院医歯薬学総合研究科, 准教授 (10218589)
MASUYAMA Ritsuko 長崎大学, 大学院医歯薬学総合研究科, 准教授 (60297596)
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| Co-Investigator(Renkei-kenkyūsha) |
MIYAZAKI Toshihiro 長崎大学, 大学院医歯薬学総合研究科, 准教授 (10174161)
MORIISHI Takeshi 長崎大学, 大学院医歯薬学総合研究科, 助教 (20380983)
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| Project Period (FY) |
2010-04-01 – 2014-03-31
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| Keywords | Runx2 / エンハンサー / 骨芽細胞 / 転写制御 / 間葉系幹細胞 |
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| Research Abstract |
Runx2 is an essential transcription factor for osteoblast differentiation at an early stage and chondrocyte differentiation at a late stage. To elucidate the mechanism of the transcriptional regulation of Runx2 gene, we generated GFP transgenic mice using the BAC clone of Runx2 gene locus. By deleting the BAC clone, we identified osteoblast-specific enhancer. The enhancer directed GFP expression specifically to osteoblasts. Dlx5/Dlx6, Mef2, Tcf7, Ctnnb1, Sp7, Smad1, and Sox5/Sox6, which localized on the enhancer region, synergistically upregulated the enhancer activity. Dlx5 and Mef2 directly bound to the enhancer, while the other factors bound to the enhancer by protein-protein interaction. Thus, Dlx5/Dlx6 and Mef2, which formed an enhanceosome with Tcf7, Ctnnb1, Sp7, Smad1, and Sox5/Sox6, play an essential role in the osteoblast-specific activation of the enhancer, leading to the differentiation of mesenchymal stem cells to osteoblasts.
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Research Products
(18 results)
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[Journal Article] Overexpression of Cdk6 and Ccnd1 in chondrocytes inhibited chondrocyte maturation and caused p53dependent apoptosis without enhancing proliferation2013
Author(s)
Ito K, Maruyama Z, Sakai A, Izumi S, Moriishi T, Yoshida CA, Miyazaki T, Komori H, Takada K, Kawaguchi H, Komori T
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Journal Title
Oncogene
Volume: Vol.33
Pages: 1862-1871
Peer Reviewed
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