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三氧化矿物凝聚体通过核因子κB信号通路促进根尖乳头干细胞的成牙本质/成骨分化及牙本质形成。

Mineral trioxide aggregate promotes the odonto/osteogenic differentiation and dentinogenesis of stem cells from apical papilla via nuclear factor kappa B signaling pathway.

作者信息

Yan Ming, Wu Jintao, Yu Yan, Wang Yanping, Xie Lizhe, Zhang Guangdong, Yu Jinhua, Zhang Chengfei

机构信息

Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, China; Endodontic Department, School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, China.

Institute of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

J Endod. 2014 May;40(5):640-7. doi: 10.1016/j.joen.2014.01.042. Epub 2014 Mar 25.

Abstract

INTRODUCTION

Mineral trioxide aggregate (MTA) has been widely used in clinical apexification and apexogenesis. However, the effects of MTA on the stem cells from apical papilla (SCAPs) and the precise mechanism of apexogenesis have not been elucidated in detail.

METHODS

Multiple colony-derived stem cells were isolated from the apical papillae, and the effects of MTA on the proliferation and differentiation of SCAPs were investigated both in vitro and in vivo. Activation of nuclear factor kappa B (NFκB) pathway in MTA-treated SCAPs was analyzed by immunofluorescence assay and Western blot.

RESULTS

MTA at the concentration of 2 mg/mL did not affect the proliferation activity of SCAPs. However, 2 mg/mL MTA-treated SCAPs presented the ultrastructural changes, up-regulated alkaline phosphatase, increased calcium deposition, up-regulated expression of odontoblast markers (dentin sialoprotein and dentin sialophosphoprotein) and odonto/osteoblast markers (runt-related transcription factor 2 and osteocalcin), suggesting that MTA enhanced the odonto/osteoblastic differentiation of SCAPs in vitro. In vivo results confirmed that MTA can promote the regular dentinogenesis of SCAPs. Moreover, MTA-treated SCAPs exhibited the up-regulated cytoplasmic phos-IκBα and phos-P65, enhanced nuclear P65, and increased nuclear translocation of P65. When co-treated with BMS345541 (the specific NFκB inhibitor), MTA-mediated odonto/osteoblastic differentiation was significantly attenuated.

CONCLUSIONS

MTA at the concentration of 2 mg/mL can improve the odonto/osteogenic capacity of SCAPs via the activation of NFκB pathway.

摘要

引言

三氧化矿物凝聚体(MTA)已广泛应用于临床根尖诱导成形术和根尖形成术。然而,MTA对根尖乳头干细胞(SCAPs)的影响以及根尖形成的确切机制尚未得到详细阐明。

方法

从根尖乳头分离出多个集落衍生干细胞,在体外和体内研究MTA对SCAPs增殖和分化的影响。通过免疫荧光分析和蛋白质印迹法分析MTA处理的SCAPs中核因子κB(NFκB)信号通路的激活情况。

结果

2mg/mL浓度的MTA不影响SCAPs的增殖活性。然而,2mg/mL MTA处理的SCAPs呈现超微结构变化,碱性磷酸酶上调,钙沉积增加,成牙本质细胞标志物(牙本质涎蛋白和牙本质涎磷蛋白)和成牙/成骨细胞标志物( runt相关转录因子2和骨钙素)的表达上调,表明MTA在体外增强了SCAPs的成牙/成骨细胞分化。体内结果证实MTA可促进SCAPs的正常牙本质形成。此外,MTA处理的SCAPs表现出细胞质磷酸化IκBα和磷酸化P65上调,核内P65增强,以及P65核转位增加。当与BMS345541(特异性NFκB抑制剂)共同处理时,MTA介导的成牙/成骨细胞分化明显减弱。

结论

2mg/mL浓度的MTA可通过激活NFκB信号通路提高SCAPs的成牙/成骨能力。

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