期刊
CELL COMMUNICATION AND SIGNALING
卷 18, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12964-020-00656-0
关键词
Angiogenesis; Cellular communication; Innervation; Matrix Metalloproteinases; Extracellular matrix Remodelling; Neurovascular interplay
类别
资金
- Agence de l'Innovation de Defense (AID)
- French National Institute of Health and Medical Research (Inserm)
- Bordeaux Consortium for Regenerative Medicine (BxCRM)
- University of Bordeaux
- Medical Research Foundation [FRM: SPF20170938783]
- Aquitaine Region [2016-1R30403]
Background 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. Methods 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. Results 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. Conclusions 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.
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