Regulation of osteoblastic differentiation by the ubiquitin-proteasome pathway and novel induction of bone formation
| Project/Area Number |
23659865
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Functional basic dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
TAMURA Masato 北海道大学, 歯学研究科(研究院), 教授 (30236757)
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| Co-Investigator(Kenkyū-buntansha) |
KAWANO Mitsuoki 新潟薬科大学, 応用生物学部, 助教 (00455338)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | プロテアソーム阻害剤 / Bortezomib / 骨芽細胞 / Wntシグナル / ユビキチンープロテアソーム系 / プロテオソーム / ユビキチン / 骨形成 / プロテアソーム |
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| Research Abstract |
Recent observations suggest that bone metabolism is regulated by the ubiquitin-proteasome pathway, and certain proteasome inhibitor has been reported to induce differentiation of osteoblasts in vitro and in vivo. In this study, we show that bortezomib induces osteoblastic differentiation and inhibits myogenic differentiation in C2C12 cells in culture. Bortezomib inhibits ubiquitin proteasome pathway to degradation of osteogenic transcriptional factor Runx2 and the function of proteasome in controlling degradation of signaling molecules in osteoblast differentiation. Bortezomib could not alter transcriptional activities of beta-catenin dependent reporter and canonical Wnt signaling target gene expression. We also demonstrated that inhibition of certain ubiquitin ligase (E3) up-regulates the differentiation of osteoblasts.
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Report
(4 results)
Research Products
(15 results)
