| Project/Area Number |
12470495
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
ITOH Nobuyuki Kyoto Univ., Grad. Sch. Pharm. Sci., Professor, 薬学研究科, 教授 (10110610)
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| Co-Investigator(Kenkyū-buntansha) |
KONISHI Morichika Kyoto Univ., Grad. Sch. Pharm. Sci., Assistant Professor, 薬学研究科, 助手 (00322165)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 2000: ¥7,100,000 (Direct Cost: ¥7,100,000)
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| Keywords | FGF / adipose / chondrocyte / bone / patter formation / gene / mouse |
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| Research Abstract |
FGFs are important intercellular signaling molecules in developmental processes. Here, we show that FGF-10 is secreted by cultured preadipocytes and prevention of FGF-10 signaling inhibits the expression of C/EBPβ and the subsequent differentiation of these cells. An active form of C/EBP rescued differentiation of the cells in which FGF-10 signaling was blocked. Development of white adipose tissue and the expression of C/EBPβ in this tissue of FGF-10 knockout mice were markedly reduced, and the ability of embryonic fibroblast derived from FGF-10 knockout mice to differentiate into adipocytes was impaired. Thus, FGF-10 plays an important role in the adipogenesis, at lest partly,by contributing to the expression of C/EBPβ thorough autocrine/paracrine mechanism.
We also demonstrate that Fgf18 is expressed in and required for osteogenesis and chondrogenesis in the mouse embryo. Fgf18 is expressed in both osteogenic mesenchymal cells and differentiating osteoblasts during calvarial bone development. In addition, Fgf18 is expressed in the perichondrium and joints of developing long bones. In calvarial bone development of Fgf18-deficient mice generated by gene targeting, the progress of suture closure is delayed. Furthermore, proliferation of calvarial osteogenic mesenchymal cells is decreased and terminal differentiation to calvarial osteoblasts is specifically delayed. Delay of osteogenic differentiation is also observed in the developing long bones of this mutant. Conversely, chondrocyte proliferation and the number of differentiated chondrocytes are increased. Thus, Fgf18 appears to regulate cell proliferation and differentiation positively in osteogenesis and negatively in chondrogenesis.
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