Research of bone formation signaling in osteoblast
| Project/Area Number |
17590961
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Kobe University |
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Principal Investigator |
KAJI Hiroshi Kobe University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (90346255)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | oateoblast / TGF-beta / Smad / Menin / bone formation / parathyroid hormone / Mineralization / 細胞分化 |
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| Research Abstract |
1 We examined the effects of parathyroid hormone (PTH), the putative potent bone forming reagent, on Smad3 and beta-catenin in osteoblastic cells. PTH and Smad3 induced the expression of beta-catenin. These actions of PTH were through both cAMP and calcium/protein kinase C systems. Moreover, PTH enhanced the transcriptional activity induced by beta-catenin. This PTH-Smad3-beta-catenin signal seemed to be associated with anti-apoptotic effects of PTH in osteoblasts. 2 We have clarified the significance of Smad3 in bone formation. Smad3 suppressed the differentiation into osteoblasts induced by bone morphogenetic protein-2 in mouse mesenchymal ST-2 cells. On the other hand, in mouse osteoblastic MC3T3-E1 cells, the induction of Smad3 on ALP activity and type I collagen expression decreased during differentiation, but the effects of Smad3 on the expressions of Runx2 and osteocalcin converted to induction from suppression during differentiation. Smad3 modulated the expression of other mineralization-related factors. 3 DNA microarray analysis with 45000 genes were performed between control and Smad3-overexpressed MC3T3-E1 cells treated with Erk1/2 inhibitor. The significance of several putative bone formation-related genes including known and unknown genes is being analyzed at the present. The expression vectors of unknown genes were made and their functions are investigated in osteoblasts. 4 MC3T3-E1 cells, which overexpressed Smad7, an inhibitory Smad, were developed. Smad7 suppressed proliferation, differentiation, the production of bone matrix proteins and mineralization in osteoblasts. Moreover, PTH induced the expression of Smad7, suggesting that Smad7 may be the target of the inhibition of bone formation.
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Report
(3 results)
Research Products
(11 results)
