FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis
FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis
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DOI：
10.1101/gad.965702
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发表时间：
2002-04-01
影响因子：
10.5
通讯作者：
Takada, S
中科院分区：
文献类型：
--
作者：
Ohbayashi, N;Shibayama, M;Takada, S
成纤维细胞生长因子信号转导参与脊椎动物骨骼的发育。成纤维细胞生长因子受体功能获得突变(FGFR)可导致颅缝融合、颅骨过早融合和侏儒症。破坏FGFR3会导致长骨和脊椎的长时间生长。然而，FGFs在胚胎骨骼发育中的实际作用尚不清楚。在这里，我们证明了Fgf18在小鼠胚胎中表达，并且是成骨和软骨形成所必需的。在颅骨发育过程中，成骨间充质细胞和分化成骨细胞均有FGF18的表达。此外，Fgf18在发育中的长骨软骨膜和关节中也有表达。在基因打靶产生的Fgf18基因缺陷小鼠的颅骨发育中，缝合的进展被推迟。此外，颅骨成骨间充质细胞的增殖减少，向颅骨成骨细胞的终末分化明显延迟。在该突变体发育中的长骨中也观察到成骨分化的延迟。相反，软骨细胞的增殖和分化的软骨细胞的数量增加。因此，FGF18在成骨过程中对细胞的增殖和分化起正向调节作用，在软骨形成过程中起负性调节作用。
Fibroblast growth factor (FGF) signaling is involved in skeletal development of the vertebrate. Gain-of-function mutations of FGF receptors (FGFR) cause craniosynostosis, premature fusion of the skull, and dwarfism syndromes. Disruption of Fgfr3 results in prolonged growth of long bones and vertebrae. However, the role that FGFs actually play in skeletal development in the embryo remains unclear. Here we show 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. Therefore, FGF18 appears to regulate cell proliferation and differentiation positively in osteogenesis and negatively in chondrogenesis.