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. This study elucidates the molecular and functional responses triggered by this intimate interaction. In this study, we showed that human dermal microvascular endothelial cells (HMEC) induced the expression of pro-angiogenic factors in stem cells from human exfoliated deciduous teeth (SHED) and sustain their osteo-differentiation at the same time. In contrast, 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 osteo-differentiation. Taken together, these findings provide novel insights into the molecular mechanism underlying the synergistic cooperation between EC and stem cells during bone tissue renewal.
Highlights
In the last two decades, countless studies have focused on the osteogenesis-angiogenesis binomial for its pivotal role in bone regeneration
The crosstalk between endothelial cell (EC) and osteoblasts is one of the key cellular interactions that underlie bone formation. This communication can occur by direct cell-cell contact or through the exchange of soluble factors with paracrine and autocrine actions
Soluble elements released at the osteogenicangiogenic interface can trigger functional responses in both cell types, supporting angiogenesis on one side and osteogenesis on the other side
Summary
In the last two decades, countless studies have focused on the osteogenesis-angiogenesis binomial for its pivotal role in bone regeneration. It has been largely demonstrated that the efficiency of the graft, in terms of bone development and of long-term graft survival, is strongly determined by the ability of the scaffold to guarantee the development of vascular networks (Mussano et al, 2018; Cipriano et al, 2020; Diomede et al, 2020) For this purpose, it is desirable to have a porous and biocompatible scaffold material with remarkable osteoinductive properties as well as a high degree of interconnectivity of the pores, which allows endothelial cell (EC) migration and proliferation and the development of a functional vascular network (Chazono et al, 2008; Chantarapanich et al, 2012; Sekiya et al, 2013; Diomede et al, 2018a). The use of co-culture systems draws much attention in bone tissue engineering (Grellier et al, 2009), investigating the intimate connection and the virtuous circuit established between angiogenic and osteogenic pathways in bone tissue renewal In this view, a deeper knowledge of the mechanisms underlying such functional relationship seems crucial for approaches aimed at bone engineering improvement
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