Role of Vascular Endothelial Growth Factor in the Communication Between Human Osteoprogenitors and Endothelial Cells

Role of Vascular Endothelial Growth Factor in the Communication Between Human Osteoprogenitors and Endothelial Cells
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DOI:
10.1002/jcb.22018
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发表时间:
2009-02-15
影响因子:
4
通讯作者:
Amedee, Joelle
Amedee, Joelle
中科院分区:
生物学2区
文献类型:
--
作者:
Grellier, Maritie;Ferreira-Tojais, Nancy;Amedee, Joelle

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适当的骨重建需要一个积极的血管生成过程,这反过来又提供了必要的生长因子和干细胞。这种组织合作表明成骨细胞和内皮细胞之间的串扰。这项工作的目的是确定通过血管内皮生长因子(VEGF)在成骨细胞和内皮细胞之间的共培养的旁分泌通信的作用。通过人骨祖细胞(HOPs)与人脐静脉内皮细胞(HUVECs)直接接触共培养模型,我们观察到HUVECs能够沿着HOPs迁移,诱导特异性管状结构的形成。VEGF(165)基因在HOPs中表达,在共培养的HOPs中表达上调,Flt-1和KDR基因在共培养的HUVECs中表达增加。然而,在共培养中观察到的细胞重排促进了可溶性化学吸引因子的组合,而不是单独的VEGF 165。尽管对内皮细胞管状样形成没有可观察到的影响,但VEGF似乎在成骨细胞分化中具有关键作用,因为其受体的抑制降低了共培养刺激的成骨细胞表型。这种共培养系统似乎可以增强原发性血管生成事件和成骨细胞分化,从而为血管化骨组织工程的新策略的发展提供了可能。J.细胞。106:390-398,2009. (C)2009 Wiley-Liss,Inc.
Proper bone remodeling requires an active process of angiogenesis which in turn supplies the necessary growth factors and stem cells. This tissue cooperation suggests a cross-talk between osteoblasts and endothelial cells. This work aims to identify the role of paracrine communication through vascular endothelial growth factor (VEGF) in co-culture between osteoblastic and endothelial cells. Through a well defined direct contact co-culture model between human osteoprogenitors (HOPs) and human umbilical vein endothelial cells (HUVECs), we observed that HUVECs were able to migrate along HOPs, inducing the formation of specific tubular-like structures. VEGF(165) gene expression was detected in the HOPs, was up-regulated in the co-cultured HOPs and both Flt-1 and KDR gene expression increased in co-cultured HUVECs. However, the cell rearrangement observed in co-culture was promoted by a combination of soluble chemoattractive factors and not by VEGF165 alone. Despite having no observable effect on endothelial cell tubular-like formation, VEGF appeared to have a crucial role in osteoblastic differentiation since the inhibition of its receptors reduced the co-culture-stimulated osteoblastic phenotype. This co-culture system appears to enhance both primary angiogenesis events and osteoblastic differentiation, thus allowing for the development of new strategies in vascularized bone tissue engineering. J. Cell. Biochem. 106: 390-398, 2009. (C) 2009 Wiley-Liss, Inc.