FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate
FGF18 is required for early chondrocyte proliferation, hypertrophy and vascular invasion of the growth plate
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DOI：
10.1016/j.ydbio.2006.08.071
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发表时间：
2007-02-01
影响因子：
2.7
通讯作者：
Ornitz, David M.
中科院分区：
文献类型：
--
作者：
Liu, Zhonghao;Lavine, Kory J.;Ornitz, David M.
成纤维细胞生长因子 18 (FGF18) 已被证明可通过 FGF 受体 3 (FGFR3) 的信号传导调节软骨细胞增殖和分化，并通过其他 FGFR 的信号传导调节骨生成。 Fgf18(-/-) 小鼠的骨骼矿化明显延迟，而 Fgfr3(-/-) 小鼠则没有这种现象。然而，这种矿化延迟不能简单地用 FGF18 向成骨细胞发出的信号来解释。在这里，我们发现Fgf18（-/-）小鼠矿化延迟与软骨细胞肥大开始延迟、软骨形成早期增殖减少、骨骼血管化延迟以及破骨细胞和成骨细胞招募至生长板延迟密切相关。我们进一步表明，FGF18 对于肥大软骨细胞和软骨膜中的 Vegf 表达是必需的，并且足以诱导骨骼外植体中的 Vegf 表达。这些发现支持这样的模型：FGF 18 通过调节软骨形成的早期阶段和 VEGF 表达来调节骨骼血管化和随后的成骨细胞/破骨细胞的募集。因此，FGF18 协调生长板的新血管形成与软骨细胞和成骨细胞的生长和分化。 (c) 2006 Elsevier Inc. 保留所有权利。
Fibroblast growth factor 18 (FGF18) has been shown to regulate chondrocyte proliferation and differentiation by signaling through FGF receptor 3 (FGFR3) and to regulate osteogenesis by signaling through other FGFRs. Fgf18(-/-) mice have an apparent delay in skeletal mineralization that is not seen in Fgfr3(-/-) mice. However, this delay in mineralization could not be simply explained by FGF18 signaling to osteoblasts. Here we show that delayed mineralization in Fgf18(-/-) mice was closely associated with delayed initiation of chondrocyte hypertrophy, decreased proliferation at early stages of chondrogenesis, delayed skeletal vascularization and delayed osteoclast and osteoblast recruitment to the growth plate. We further show that FGF18 is necessary for Vegf expression in hypertrophic chondrocytes and the perichondrium and is sufficient to induce Vegf expression in skeletal explants. These findings support a model in which FGF 18 regulates skeletal vascularization and subsequent recruitment of osteoblasts/osteoclasts through regulation of early stages of chondrogenesis and VEGF expression. FGF18 thus coordinates neovascularization of the growth plate with chondrocyte and osteoblast growth and differentiation. (c) 2006 Elsevier Inc. All rights reserved.