| Project/Area Number |
16591996
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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 |
Surgical dentistry
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| Research Institution | Okayama University |
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Principal Investigator |
YAMACHIKA Eiki Okayama University, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (10294422)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJIGIWA Hidetsugu Okayama University, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (70335628)
FUKUNAGA Joji Okayama University, Graduate school of Medicine, Dentistry and Pharmaceutical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 助手 (10284069)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | BMP / Cytokine / Immobilization / bone / Regeneration / BMP-2 / I型アテロコラーゲン / 細胞活性 / 細胞内シグナル伝達 / Smad |
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| Research Abstract |
Bone morphogenetic protein 2(BMP-2) plays an important role in bone growth and regeneration. The creation of purified recombinant human BMP-2 (rhBMP-2) has led to advances in its potential for clinical use, however this protein is soluble and disperses soon after implantation. So rhBMP-2 can't have long time stimulation to BMP signaling cascade. To overcome this problem we reported the effects of immobilization of rhBMP-2 to succinylated type I atelocollagen
The mechanism of immobilized rhBMP-2 is based on the theories of covalent bonding between rhBMP-2 and succinylated type I atelocollagen. The immobilized rhBMP-2 binds with the receptor on the cell surface without being internalized into the cell, so it is able to transduce signals into the cell over a long period of time, achieving high efficiency in promoting cell proliferation.
We investigated the effect of immobilized rhBMP-2 by the way of (a) histological findings, (b) alkaline phosphatase (ALP) activity, (c) BMP intracellular signaling cascade (Smad1, Smad5 and phospho Smad1/5/8) expression, and (d) type I collagen, osteonectin, osteopontin, ostocalcin, and Smad1/5/8 mRNA expression.
Our results showed that (1) nonimmobilized and immobilized rhBMP-2 also increased the alkaline phosphatase (ALP) activity in ST2, MC3T3 and C2C12 cells. However significantly higher ALP activity was observed by the immobilized rhBMP-2 treatment. (2) Phosphorylation of Smad1/5/8 after nonimmobilized rhBMP-2 stimulation increased from 15 min after stimulation and decrease to the control revel after 6hrs, however the phosphorylation was prolonged by immobilized rhBMP-2 and its effect was detectable even after 48hrs.
So we conclude that because immobilized rhBMP-2 can emphasize and prolonged the effect of rhBMP-2, immobilizing rhBMP-2 is an efficient method to increase bone induction.
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