Analysis of Transcription Factor Network Regulating Skeletogenesis
| Project/Area Number |
17390493
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NAKASHIMA Kazuhisa Tokyo Medical and Dental University, Medical Research Institute, COE-Professor (90252692)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,470,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2007: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2006: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2005: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | Osteoblast / Differentiation / Transcription Factor / Skeletogenesis / BMP / Osterix / 破骨細胞 / 骨格 / パターニング / Schnurri-2 / マウス遺伝学 / 骨形成 |
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| Research Abstract |
We previously identified a bone specific transcription factor Osterix (Osx) that appeared to be an essential regulator of osteoblast differentiation along with another key transcription factor Runx2/Cbfa1, although the mechanisms of the regulation for osteoblast differentiation and the skeletogenesis have not been clarified in detail so far. We thus hypothesized the existence of the transcription factor network that would orchestrate the developmental machinery of those processes, and to understand the reality of the hypothesis, we investigated putative factors involved in the network. The factors include Runx2, Cnot7, Schumurri-2 and Ciz which were supposed to contribute to the Osterix-related regulatory pathways. By analyzing null-mutant mice deficient for these factors, we revealed molecular involvement of each factor for cell signaling and bone formation through their actions on osteoblasts in various way. In these studies, we mainly focused on the pathways stimulated by humoral factors that activates osteoblast function, including bone morphogenetic proteins (BMPs) and parathyroid hormone (PTH). In addition, we investigated novel aspects of osteoblastic differentiation, through mechanisms of molecular pathways related to transcription factors JunD and NfatC1, or by patterning signal molecule PlexinD1, a cation-channel Trpv4, and rennin-angiotensin system (RAS) using gene targeting disruption of the experimental mice. Although the entire picture of the transcription factor network is still unveiled, our study indicated possible involvement of multiple factors in the machinery, clarification of which would be beneficial for developing application methods for related clinical situations.
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Report
(4 results)
Research Products
(59 results)
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[Journal Article] Transient Receptor Potential Vanilloid 4 Deficiency Suppresses Unloading-Induced Bone Loss.2008
Author(s)
Mizoguchi F., Mizuno A., Hayata T., Nakashima K., Heller S., Ushida T., Sokabe M., Miyasaka N., Suzuki M., Ezura Y., Noda M.
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Journal Title
Journal of Cellular Physiology. 216
Pages: 47-53
Related Report
Peer Reviewed
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[Journal Article] Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors.2005
Author(s)
Haruhiko Akiyama, Jung-Eun Kim, Kazuhisa Nakashima, Gener Balmes, Naomi Iwai, Jian Min Deng, Zhaoping Zhang, James F.Martin, Richard R.Behringer, Takashi Nakamura, Benoit de Crombrugghe.
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Journal Title
Proc.Natl.Acad.Sci.USA. 102(41)
Pages: 14665-14670
Related Report
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[Journal Article] NFAT and Osterix cooperatively regulate bone formation.2005
Author(s)
Koga, T., Matsui, Y., Kodama, T., de Crombrugghe, B., Nakashima, K., Takayanagi, H.
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Journal Title
Nat Med. 11(8)
Pages: 880-885
Related Report
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[Presentation] Osteoclast Specific Ablation of Dicer Suppresses Bone Resorption and Increases Bone Mass2007
Author(s)
Mizoguchi F., Nakamura T., Hayata T., Hemmi H., Ezura Y., Nakashima K., Miyasaka N., Harfe B., Kato S., Noda M.
Organizer
The 29th Annual Meeting of American Society for Bone and Mineral Research
Place of Presentation
Honolulu, Hawaii
Related Report
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[Presentation] β-adrenergic Signaling Requires Bone Matrix Protein OPN to Suppress Bone Formation and to Activate Bone Resorption2007
Author(s)
Nagao M., Saita Y., Nagata J., Izu Y., Hayata T., Hemmi H., Ezura Y., Nakashima K., Kurosawa H., Noda M.
Organizer
The 29th Annual Meeting of American Society for Bone and Mineral Research
Place of Presentation
Honolulu, Hawaii
Related Report
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[Presentation] β2 Adrenergic Receptor Deficiency Enhances Bone Mass in by Antagonizing Against Aging-induced Bone Loss and Blunts Anabolic Effects of PTH on Osteoblasts2007
Author(s)
Hanyu R., Saita Y., Nagata J., Izu Y., Hayata T., Hemmi H., Takeda S., Ezura Y., Nakashima K., Kurosawa H., Noda M.
Organizer
The 29th Annual-Meeting of American Society for Bone and Mineral Research
Place of Presentation
Honolulu, Hawaii
Related Report
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