Role of HIF-1alpha in skeletal development.
Role of HIF-1alpha in skeletal development.
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DOI：
10.1111/j.1749-6632.2009.05238.x
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发表时间：
2010-03
影响因子：
5.2
通讯作者：
Clemens TL
中科院分区：
文献类型：
--
作者：
Wan C;Shao J;Gilbert SR;Riddle RC;Long F;Johnson RS;Schipani E;Clemens TL
在骨的发育和再生过程中，血管生成和骨生成是紧密耦合的。间充质细胞在发育中的基质中引发血管生成信号以募集新血管进入骨。可能从传入的血管内皮发出的相互信号通过与血管干细胞龛内的细胞的额外相互作用刺激间充质细胞特化。低氧诱导因子-1 α（HIF-1）通路已被确定为该过程中的关键组分。我们证明，HIF-1在成熟成骨细胞中的过度表达，通过破坏von Hippel-Lindau蛋白，大大增加了血管生成和骨生成;这些过程似乎是由细胞非自主机制耦合的，涉及血管内皮生长因子（VEGF）对内皮细胞的作用。损伤介导的骨再生（牵张成骨）模型中也发生了同样的情况。令人惊讶的是，HIF-1的操作不影响颅骨的血管生成，其中在颅骨形成期间，冷凝间充质中HIF-1的早期激活上调osterix。
Angiogenesis and osteogenesis are tightly coupled during bone development and regeneration. Mesenchymal cells in the developing stroma elicit angiogenic signals to recruit new blood vessels into bone. Reciprocal signals, likely emanating from the incoming vascular endothelium, stimulate mesenchymal cell specification through additional interactions with cells within the vascular stem cell niche. The hypoxia-inducible factor-1 alpha (HIF-1) pathway has been identified as a key component in this process. We demonstrated that overexpression of HIF-1 in mature osteoblasts through disruption of the von Hippel-Lindau protein profoundly increases angiogenesis and osteogenesis; these processes appear to be coupled by cell nonautonomous mechanisms involving the action of vascular endothelial growth factor (VEGF) on the endothelial cells. The same occurred in the model of injury-mediated bone regeneration (distraction osteogenesis). Surprisingly, manipulation of HIF-1 does not influence angiogenesis of the skull bones, where earlier activation of HIF-1 in the condensing mesenchyme upregulates osterix during cranial bone formation.
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影响因子：
4.7
作者：
Riddle, Ryan C.;Khatri, Richa;Schipani, Ernestina;Clemens, Thomas L.
通讯作者：
Clemens, Thomas L.
影响因子：
64.5
作者：
Sacchetti, Benedetto;Funari, Alessia;Bianco, Paolo
通讯作者：
Bianco, Paolo
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
2.6
作者：
Maes, C;Carmeliet, P;Carmeliet, G
通讯作者：
Carmeliet, G
影响因子：
6
作者：
Chang, H;Shyu, KG;Kuan, PL
通讯作者：
Kuan, PL