首页> 外文期刊>Journal of cellular biochemistry. >Vascular endothelial growth factor (VEGF-A) expression in human mesenchymal stem cells: autocrine and paracrine role on osteoblastic and endothelial differentiation.
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Vascular endothelial growth factor (VEGF-A) expression in human mesenchymal stem cells: autocrine and paracrine role on osteoblastic and endothelial differentiation.

机译:人间充质干细胞中的血管内皮生长因子(VEGF-A)表达:自分泌和旁分泌对成骨细胞和内皮细胞分化的作用。

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摘要

Angiogenesis is essential in bone fracture healing for restoring blood flow to the fracture site. Vascular endothelial growth factor (VEGF) and its receptor have been implicated in this process. Despite the importance of angiogenesis for the healing processes of damaged bones, the role of VEGF signaling in modulation of osteogenic differentiation in human mesenchymal stem cells has not been investigated in great detail. We examined the expression of VEGF-A and VEGFR-1 in human adult mesenchymal stem cells derived from trabecular bone (hTBCs). VEGF-A was found to be secreted in a differentiation dependent manner during osteogenesis. Transcripts for VEGF-A were also seen to be elevated during osteogenesis. In addition, transcripts for VEGF-A and the corresponding receptor VEGFR-1 were upregulated under hypoxic conditions in undifferentiated hTBCs. To investigate the signaling of VEGF-A on osteogenesis recombinant hTBCs were generated. High expression of VEGF-A stimulated mineralization, whereas high expression of sFLT-1, an antagonist to VEGF-A, reduced mineralization suggesting that VEGF-A acts as autocrine factor for osteoblast differentiation. In addition, VEGF-A secreted by hTBCs promotes sprouting of endothelial cells (HUVE) demonstrating a paracrine role in blood vessel formation. In summary, an in vitro analysis of transgene effects on cellular behavior can be used to predict an effective ex vivo gene therapy.
机译:在骨折愈合中,血管生成对于恢复流向骨折部位的血流至关重要。血管内皮生长因子(VEGF)及其受体已牵涉到此过程。尽管血管生成对于受损骨骼的愈合过程非常重要,但尚未详细研究VEGF信号传导在人间充质干细胞中成骨分化的调节中的作用。我们检查了源自小梁骨(hTBCs)的人成人间充质干细胞中VEGF-A和VEGFR-1的表达。发现在成骨过程中以分化依赖性方式分泌VEGF-A。 VEGF-A的转录本在成骨过程中也被发现升高。此外,在缺氧条件下,未分化的hTBCs中VEGF-A和相应的受体VEGFR-1的转录物被上调。为了研究VEGF-A对成骨的信号传导,产生了重组hTBC。 VEGF-A的高表达刺激了矿化作用,而VEGF-A的拮抗剂sFLT-1的高表达降低了矿化作用,提示VEGF-A充当成骨细胞分化的自分泌因子。此外,hTBCs分泌的VEGF-A促进内皮细胞(HUVE)的萌发,表明旁分泌在血管形成中发挥作用。总之,转基因对细胞行为影响的体外分析可用于预测有效的离体基因治疗。

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