| Project/Area Number |
17592086
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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 | HIROSHIMA UNIVERSITY |
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Principal Investigator |
WANG Hua HIROSHIMA UNIVERSITY, Graduate school of Biomedical Science, Assistant, 大学院医歯薬学総合研究科, 助手 (50363081)
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| Co-Investigator(Kenkyū-buntansha) |
ZHANG Yan HIROSHIMA UNIVERSITY, Graduate School of Biomedical Science, Assistant, 大学院医歯薬学総合研究科, 助手 (50332797)
YOSHIKO Yuji HIROSHIMA UNIVERSITY, Graduate School of Biomedical Science, Associate Professor, 大学院医歯薬学総合研究科, 助教授 (20263709)
MAEDA Norihiko HIROSHIMA UNIVERSITY, Graduate School of Biomedical Science, Professor, 大学院医歯薬学総合研究科, 教授 (60049418)
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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 |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Tie2 / Angiopoietin / Haemangioma / Angiosarcoma / Fibrous growth factor 23 / Hemangioma / Angiosarcoma |
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| Research Abstract |
Tie2, an endothelium-specific receptor tyrosine kinase, plays a central role in controlling vascular homeostasis. We previous findings that a mutation G833D in ATP-binding domain of Tie2 (Tie2_<G833D>) from human benign haemangiomas has mitogenic and transforming potentialities are extended by the current study. Indeed, murine vascular endothelial cell lines overexpressing Tie2_<G833D> (MSS31G833D) displayed the typical features of neoplastic transformation: the cell lost cell-cell contact inhibition, increased the expressions of PCNA (proliferating cell nuclear antigen), and angiosarcoma developed in nude mice. Notably, We found that Ang2 could effectively block Ang1 activation of wild-type Tie2 and Q837H Tie2, but failed to inhibit Ang1-induced Tie2G833D autophosphorylation. Osteomalacia often occurs in vascular tumors, including haemangioma and angiosarcoma. It has been reported that fibroblast growth factor 23 (FGF23), a secreted peptide hormone, overproduced in patients with tumor
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induced osteomalacia. Thus, we examined expression of FGF23 in these transfectants. Real-time PCR showed that MSS31G833D cells expressed FGF23 mRNA more than does control cells. To invest role of FGF23 in osteomalacia, we constructed recombinant adenovirus-human FGF23 (AV-FGF23) by using the Adeno-X^<TM> expression system and assessed the effects of FGF23 overexpression during osteoblast development and matrix mineralization in the RC model. Infection of proliferating cells with AV-FGF23 did not significantly affect cell growth as compared to cells infected with control adenovirus. However, we found that cells overexpressing FGF23 made fewer and smaller nodules than control cultures with a parallel decrease in levels of osteoblast differentiation marker mRNAs. Furthermore, FGF23 overexpression inhibited osteoid nodule mineralization in the presence of β-glycerophosphate. Thus, we conclude that G833D mutant may escape the negative regulation of Ang2 on the receptor and result in elevation of FGF23 expression. FGF23 may act as a local negative regulator of osteoblast development and matrix mineralization. Less
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