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血管内皮生长因子A(VEGFA)通过细胞外信号调节激酶(ERK)/p38信号通路促进牙髓干细胞向成牙本质/成骨细胞分化。

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

作者信息

Okada Yamato, Kawashima Nobuyuki, Noda Sonoko, Murano Hiroki, Han Peifeng, Hashimoto Kentaro, Kaneko Tomoatsu, Okiji Takashi

机构信息

Department of Pulp Biology and Endodontics, Division of Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.

Department of Pulp Biology and Endodontics, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan.

出版信息

J Dent Sci. 2025 Jul;20(3):1590-1597. doi: 10.1016/j.jds.2022.08.013. Epub 2022 Aug 30.

Abstract

UNLABELLED

: 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 . This study also aimed to examine the mineralized tissue-forming and pro-angiogenic potentials of VEGFA in rat dental pulp .

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 ; it promotes mineralized tissue formation and neovascularization in pulp tissue .

摘要

未标记

血管内皮生长因子A(VEGFA)是一种强大的血管生成因子,也是血管内皮细胞的重要生长因子,但其对牙髓干细胞(如人脱落乳牙干细胞,SHEDs)的影响尚未得到充分评估。本研究的目的是探讨VEGFA对SHEDs中牙本质/成骨细胞分化的影响及其潜在机制。本研究还旨在研究VEGFA在大鼠牙髓中形成矿化组织和促血管生成的潜力。

材料与方法

用重组人VEGFA(rhVEGFA)刺激SHEDs后,评估其增殖、迁移、牙本质/成骨细胞基因表达和矿化结节形成情况。通过蛋白质印迹法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。在暴露于rhVEGFA浸泡的琼脂糖珠10天后,对大鼠磨牙牙髓进行组织学和免疫组织化学检查。

结果

rhVEGFA刺激促进了SHEDs的迁移、牙本质/成骨细胞标志物RUNX家族转录因子2(RUNX2)和碱性磷酸酶(ALP)的mRNA表达以及矿化结节形成;ERK和p38/MAPK抑制剂可降低这些作用。经rhVEGFA处理的大鼠磨牙牙髓组织表现出类似修复性牙本质的矿化组织,周围有巢蛋白阳性细胞和密集分布的CD146血管。

结论

rhVEGFA可通过ERK/p38信号通路促进SHEDs的迁移、牙本质/成骨细胞分化和矿化结节形成;它促进牙髓组织中的矿化组织形成和新血管形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/12254764/1a2c91c81029/gr1.jpg

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