Vegfa regulates perichondrial vascularity and osteoblast differentiation in bone development
Vegfa regulates perichondrial vascularity and osteoblast differentiation in bone development
复制标题
DOI：
10.1242/dev.117952
复制
发表时间：
2015-06-01
期刊：
影响因子：
4.6
通讯作者：
Berendsen, Agnes D.
中科院分区：
文献类型：
--
作者：
Duan, Xuchen;Murata, Yurie;Berendsen, Agnes D.
血管内皮生长因子 A (Vegfa) 在软骨内骨形成中发挥重要作用。成骨细胞前体、内皮细胞和破骨细胞响应（前）肥大软骨细胞分泌的 Vegfa，从软骨膜迁移到未来骨骼软骨模板的初级骨化中心。软骨膜骨系细胞也产生 Vegfa，但其功能尚不清楚。通过删除体内骨系细胞中的 Vegfa，我们证明祖细胞衍生的 Vegfa 是软骨膜中血管募集和小鼠成骨细胞前体分化所必需的。 Vegfa 受体的条件性缺失表明 Vegfa 依赖性对成骨细胞分化的影响是由 Vegf 受体 2 (Vegfr2) 介导的。此外，Vegfa/Vegfr2 信号传导刺激印度刺猬蛋白的表达和活性，增加 β-catenin 的表达并抑制 Notch2。我们的研究结果表明，Vegfa 是骨骼发育早期阶段软骨膜血管分布和成骨细胞分化的调节剂。
Vascular endothelial growth factor A (Vegfa) has important roles in endochondral bone formation. Osteoblast precursors, endothelial cells and osteoclasts migrate from perichondrium into primary ossification centers of cartilage templates of future bones in response to Vegfa secreted by (pre) hypertrophic chondrocytes. Perichondrial osteolineage cells also produce Vegfa, but its function is not well understood. By deleting Vegfa in osteolineage cells in vivo, we demonstrate that progenitor-derived Vegfa is required for blood vessel recruitment in perichondrium and the differentiation of osteoblast precursors in mice. Conditional deletion of Vegfa receptors indicates that Vegfa-dependent effects on osteoblast differentiation are mediated by Vegf receptor 2 (Vegfr2). In addition, Vegfa/Vegfr2 signaling stimulates the expression and activity of Indian hedgehog, increases the expression of beta-catenin and inhibits Notch2. Our findings identify Vegfa as a regulator of perichondrial vascularity and osteoblast differentiation at early stages of bone development.