Basic research for phosphaturic factors including FGF23 as molecular targets for clinical applications.
| Project/Area Number |
18592001
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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 |
Morphological basic dentistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
YOSHIKO Yuji Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (20263709)
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| Co-Investigator(Kenkyū-buntansha) |
WANG Hua Hiroshima University, Graduate School of Biomedical Sciences, Assistant Professor (50363081)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Bone mineralization / Osteoblasts / FGF23 / Phosphaturic factor / NaPi cotransporter / Pit 1 / Pit1 / 骨形成 / 歯の形成 / くる病・骨軟化症 / 低リン血症 / 無機リン酸 / Phex / マイクロアレイ |
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| Research Abstract |
The complex pathogenesis of mineralization defects seen in inherited and/or acquired hypophosphatemic disorders suggests that local phosphate (Pi) regulation and Pi-regulating factors including fibroblast growth factor (FGF) 23 by osteoblasts may be a rate-limiting step in physiological bone mineralization. By using multiple rat models, we established following results.
1. We manipulated well-established in vivo and in vitro models to study bone mineralization stages separately from cellular proliferation/differentiation stages of osteogenesis.
2. Sodium-dependent phosphate (NaPi) cotransport in osteoblasts was crucial for bone mineralization by using foscarnet, a selecitive NaPi cotransporter independently of systemic Pi levels.
3. Amongst multiple sodium-dependent Pi (Nan) cotranspoters identified, bone mineralization was down-and upregulated respectively with under- and overexpression of the type III NaPi transporter Pitl in osteoblast cultures.
4. FGF23 was expressed most abundantly in skeletal cells and dental cells. We overexpressed FGF23 in osteoblasts by using the adenoviral overexpression system, resulting in bone mineralization defects dependently of tyrosine phosphorylation of FGF receptor.
These results provide new insights into the functional role Pi-regulating factors of osteoblasts in bone mineralization, whose manipulations may be useful for hypophosphatemic and other skeletal and dental disorders.
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Report
(3 results)
Research Products
(17 results)
