VEGF-A and PlGF-1 stimulate chemotactic migration of human mesenchymal progenitor cells

VEGF-A and PlGF-1 stimulate chemotactic migration of human mesenchymal progenitor cells
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DOI:
10.1016/j.bbrc.2005.06.116
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发表时间:
2005-08-26
影响因子:
3.1
通讯作者:
Brenner, RE
Brenner, RE
中科院分区:
生物学4区
文献类型:
--
作者:
Fiedler, J;Leucht, F;Brenner, RE

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血管内皮生长因子(VEGF)已被证明在软骨内成骨过程中发挥作用,通过刺激血管侵入肥大软骨,导致其被小梁骨取代。我们可以证明VEGF-A和PIGF-1对人间充质祖细胞具有剂量依赖性的化学吸引作用,而VEGF-E或VEGF-C则没有。实时荧光定量PCR结果显示,vegfr -1 (Flt-1)、VEGFR-2 (KDR/Flk-1)和VEGFR-3 (Flt-4)的表达在成骨分化过程中明显下降。RT-PCR检测neuropilin-1和-2的表达。在体外激酶试验中,我们可以证明在特定配体的刺激下,vegfr - 1和VEGFR-2被激活。这些发现与以下观点一致:VEGF-A对MPC的趋化作用是通过VEGFR-1介导的,VEGF-A和PIGF-1在软骨内骨形成或重塑过程中具有骨祖细胞募集的功能作用。(c) 2005爱思唯尔公司版权所有。
Vascular endothelial growth factor (VEGF) has been indicated to play a role during endochondral ossification by stimulation of blood vessel invasion into hypertrophic cartilage resulting in its replacement by trabecular bone. We could demonstrate a dose-dependent chemoattractive effect of VEGF-A and PIGF-1, but not VEGF-E or VEGF-C, on human mesenchymal progenitor cells. Quantitative realtime PCR revealed the expression of VEGFR-I (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4), which markedly declined during osteogenic differentiation. In addition, expression of neuropilin-1 and -2 was detected by RT-PCR. In an in vitro kinase assay, we could demonstrate activation of VEGFR-I and VEGFR-2 upon stimulation with specific ligands. These findings are consistent with the idea that the chemotactic effect of VEGF-A on MPC is mediated via VEGFR-1, and that VEGF-A and PIGF-1, have a functional role for recruitment of osteoprogenitor cells in the course of endochondral bone formation or remodeling. (c) 2005 Elsevier Inc. All rights reserved.