| Project/Area Number |
20592139
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Morphological basic dentistry
|
|---|
| Research Institution | Hiroshima University |
|---|
Principal Investigator |
YOSHIKO Yuji Hiroshima University, 大学院・医歯薬学総合研究科, 准教授 (20263709)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MINAMIZAKI Tomoko 広島大学, 医歯薬学総合研究科, 助教 (30452593)
UCHIDA Soshi 産業医科大学, 医学部, 助教 (60330990)
YOSHIOKA Hirotaka 広島大学, 医歯薬学総合研究科, 助教 (50523411)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Keywords | GF23 / Klotho / 石灰化 / マップキナーゼ(ERK) / FGF23 / 可溶型Klotho / 骨芽細胞 / 可溶化Klotho(細胞外ドメイン) / 歯・骨の石灰化 / マウス / KLotho / ERK |
|---|
| Research Abstract |
Fibroblast growth factor 23 (FGF23) acts as a phosphaturic hormone upon 1α, 25-dihydroxyvitamin D_3 (1,25(OH)_2D_3) stimulation, and the truncated form (sKL) of Klotho, a coreceptor for FGF23 in kidney, is released into the circulation. Here, we show that an intravenous injection of sKL rapidly increases ERK phosphorylation as FGF23 signaling in bone but not in kidney in mice, when preloaded with 1,25(OH)_2D_3. The unique activity of sKL in bone is mimicked in Klotho-deficient mutant (kl/kl) mice, in spite of the kl/kl high serum concentrations of phosphate, calcium, 1,25(OH)_2D_3 and FGF23. These mice exhibit selective accumulation of FGF23 and sKL and subsequent hypomineralization in parietal bone, without changes in serum parameters examined. sKL in serum is necessary for complex formation with FGF23 and the corresponding hypomineralization effects in osteoblast/osteocyte cultures, when FGF23 levels are increased by 1,25(OH)_2D_3. These data define a novel bone-kidney axis in which sKL acts as a cofactor for FGF23 in parietal bone, and the unique bone milieu mediates the local actions of FGF23.
|
