AUTHOR=Petrillo Sara , Genova Tullio , Chinigò Giorgia , Roato Ilaria , Scarpellino Giorgia , Kopecka Joanna , Altruda Fiorella , Tolosano Emanuela , Riganti Chiara , Mussano Federico , Munaron Luca 

TITLE=Endothelial Cells Promote Osteogenesis by Establishing a Functional and Metabolic Coupling With Human Mesenchymal Stem Cells

JOURNAL=Frontiers in Physiology

VOLUME=Volume 12 - 2021

YEAR=2022

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.813547

DOI=10.3389/fphys.2021.813547

ISSN=1664-042X

ABSTRACT=Bone formation involves a complex crosstalk between endothelial cells (EC) and osteodifferentiating stem cells. This functional interplay is greatly mediated by the paracrine and autocrine action of soluble factors released at the vasculature-bone interface. The aim of this study was to elucidate the molecular and functional responses triggered by this intimate interaction. Here, we showed that human dermal microvascular endothelial cells (HMEC) induced the expression of pro-angiogenic factors in human exfoliated deciduous teeth stem cells (SHED) and sustain their osteodifferentiation at the same time. On the other hand, osteodifferentiating SHED increased EC recruitment and promoted the formation of complex vascular networks. Moreover, HMEC enhanced anaerobic glycolysis in proliferating SHED without compromising their ability to undergo the oxidative metabolic shift required for adequate osteodifferentiation. Taken together, these findings provide novel insights on the molecular mechanism underlying the synergistic cooperation between EC and stem cells during bone tissue renewal.