VEGFA promotes odonto/osteoblastic differentiation in dental pulp stem cells via ERK/p38 signaling

Abstract

Background/purpose: Vascular endothelial growth factor A (VEGFA) is a potent angiogenic factor and an essential growth factor for vascular endothelial cells, but its effects on dental pulp stem cells, such as stem cells from human exfoliated deciduous teeth (SHEDs), have not been fully evaluated. The aim of this study was to explore the effects and underlying mechanisms of VEGFA on odonto/osteoblastic differentiation in SHEDs in vitro. This study also aimed to examine the mineralized tissue-forming and pro-angiogenic potentials of VEGFA in rat dental pulp in vivo. Materials and methods: Proliferation, migration, odonto/osteoblastic gene expression, and mineralized nodule formation were evaluated in SHEDs after stimulation with recombinant human VEGFA (rhVEGFA). Expression patterns of extracellular signal-regulated kinase (ERK) and p38/mitogen-activated protein kinase (MAPK) were analysed by western blotting. Rat molar pulp was histologically and immunohistochemically examined after 10 days of rhVEGFA-soaked agarose bead exposure. Results: rhVEGFA stimulation promoted migration, mRNA expression of odonto/osteoblastic markers RUNX family transcription factor 2 (RUNX2) and alkaline phosphatase (ALP), and mineralized nodule formation in SHEDs; these effects were reduced by ERK and p38/MAPK inhibitors. RhVEGFA-treated rat molar pulp tissues exhibited a reparative dentin-like mineralized tissue with surrounding nestin-positive cells and densely distributed CD146+ vascular vessels. Conclusion: rhVEGFA can promote migration, odonto/osteoblastic differentiation, and mineralized nodule formation via ERK/p38 signaling in SHEDs in vitro; it promotes mineralized tissue formation and neovascularization in pulp tissue in vivo.

Keywords

• Extracellular signal-regulated kinases
• Dentinogenesis
• p38 mitogen-activated protein kinases
• Mesenchymal stem cells
• Vascular endothelial growth factor A