Univ. Bordeaux, INSERM, BIOTIS, U1026, F-33000, Bordeaux, France.
Univ. Bordeaux, CNRS, Solvay, LOF, UMR 5258, F-33006, Pessac, France.
Cell Commun Signal. 2020 Oct 19;18(1):162. doi: 10.1186/s12964-020-00656-0.
Recent physiological and experimental data highlight the role of the sensory nervous system in bone repair, but its precise role on angiogenesis in a bone regeneration context is still unknown. Our previous work demonstrated that sensory neurons (SNs) induce the osteoblastic differentiation of mesenchymal stem cells, but the influence of SNs on endothelial cells (ECs) was not studied.
Here, in order to study in vitro the interplay between SNs and ECs, we used microfluidic devices as an indirect co-culture model. Gene expression analysis of angiogenic markers, as well as measurements of metalloproteinases protein levels and enzymatic activity, were performed.
We were able to demonstrate that two sensory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P (SP), were involved in the transcriptional upregulation of angiogenic markers (vascular endothelial growth factor, angiopoietin 1, type 4 collagen, matrix metalloproteinase 2) in ECs. Co-cultures of ECs with SNs also increased the protein level and enzymatic activity of matrix metalloproteinases 2 and 9 (MMP2/MMP9) in ECs.
Our results suggest a role of sensory neurons, and more specifically of CGRP and SP, in the remodelling of endothelial cells extracellular matrix, thus supporting and enhancing the angiogenesis process. Video abstract.
最近的生理学和实验数据强调了感觉神经系统在骨修复中的作用，但它在骨再生背景下对血管生成的确切作用仍不清楚。我们之前的工作表明，感觉神经元（SNs）诱导间充质干细胞的成骨分化，但没有研究 SNs 对内皮细胞（ECs）的影响。
为了研究 SNs 和 ECs 之间的相互作用，我们在体外使用微流控装置作为间接共培养模型。进行了血管生成标记物的基因表达分析，以及金属蛋白酶蛋白水平和酶活性的测量。
我们能够证明两种感觉神经肽，降钙素基因相关肽（CGRP）和 P 物质（SP），参与了 ECs 中转录上调血管生成标记物（血管内皮生长因子、血管生成素 1、4 型胶原、基质金属蛋白酶 2）的过程。ECs 与 SNs 的共培养还增加了 ECs 中基质金属蛋白酶 2 和 9（MMP2/MMP9）的蛋白水平和酶活性。
我们的结果表明感觉神经元，更具体地说是 CGRP 和 SP，在重塑内皮细胞细胞外基质中起作用，从而支持和增强血管生成过程。视频摘要。
