VEGFA promotes odonto/osteoblastic differentiation in dental pulp stem cells via ERK/p38 signaling
VEGFA promotes odonto/osteoblastic differentiation in dental pulp stem cells via ERK/p38 signaling
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DOI：
10.1016/j.jds.2022.08.013
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发表时间：
2022-08
影响因子：
3.5
通讯作者：
Y. Okada;N. Kawashima;S. Noda;Hiroki Murano;Peifeng Han;K. Hashimoto;T. Kaneko;T. Okiji
中科院分区：
文献类型：
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作者：
Y. Okada;N. Kawashima;S. Noda;Hiroki Murano;Peifeng Han;K. Hashimoto;T. Kaneko;T. Okiji
背景/目的：血管内皮生长因子A（VEGFA）是一种强有力的血管生成因子和血管内皮细胞的必需生长因子，但其对牙髓干细胞（如来自人脱落乳牙（SHED）的干细胞）的作用尚未得到充分评价。本研究旨在探讨VEGFA对体外培养的SHED成牙/成骨细胞分化的影响及其机制。本研究还旨在研究矿化组织形成和促血管生成的VEGFA在大鼠牙髓vivo.Materials和methodsProliferation，迁移，牙/成骨细胞基因表达，矿化结节形成后，重组人VEGFA（rhVEGFA）刺激SHEDs进行了评价。Western blotting分析细胞外信号调节激酶（ERK）和p38/丝裂原活化蛋白激酶（MAPK）的表达模式。大鼠磨牙牙髓组织学和免疫组化检查后10天的rhVEGF浸泡的琼脂糖bead exposure. ResultsrhVEGF刺激促进迁移，mRNA表达的牙/成骨细胞标记RUNX家族转录因子2（RUNX 2）和碱性磷酸酶（ALP），并矿化结节形成SHEDs;这些影响减少ERK和p38/MAPK抑制剂。结论rhVEGFA在体外可通过ERK/p38信号通路促进牙髓组织迁移、成牙/成骨细胞分化和矿化结节形成;在体内可促进牙髓组织矿化和新生血管形成。
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 SHEDsin vitro. This study also aimed to examine the mineralized tissue-forming and pro-angiogenic potentials of VEGFA in rat dental pulpin vivo.Materials and methodsProliferation, 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.ResultsrhVEGFA 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.ConclusionrhVEGFA can promote migration, odonto/osteoblastic differentiation, and mineralized nodule formation via ERK/p38 signaling in SHEDsin vitro; it promotes mineralized tissue formation and neovascularization in pulp tissuein vivo.