Journal Article

Sensory neurons from dorsal root ganglia regulate endothelial cell function in extracellular matrix remodelling

Leroux, Alice, Oliveira, Hugo, Leng, Jacques, Paiva dos Santos, Bruno, Amédée, Joëlle

2020

Overview

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. 2_7KgRKy4YATrqDcNKG8uB Video abstract

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Angiogenesis / Angiopoietin / Biomedical and Life Sciences / Bone growth / Bone healing / Bone marrow / Calcitonin / Calcitonin gene-related peptide / Cell Biology / Cell culture / Cell differentiation / Cellular communication / Chemical Physics / Collagen / Condensed Matter / Cytokines and Growth Factors / Dorsal root ganglia / Endothelial cells / Enzymatic activity / Extracellular matrix / Extracellular matrix Remodelling / Gelatinase A / Gelatinase B / Gene expression / Innervation / Life Sciences / Materials Science / Matrix metalloproteinase / Matrix Metalloproteinases / Mesenchyme / Microfluidics / Neuropeptides / Neurosciences / Neurovascular interplay / Osteoblastogenesis / Peptides / Physics / Protein-Ligand Interactions / Receptors / Sensory neurons / Skin / Soft Condensed Matter / Stem cells / Transcription / Vascular endothelial growth factor / Wound healing