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唾液酸通过增强MAPK/ERK信号通路激活诱导人牙髓干细胞向成骨/成牙本质细胞分化

Neu5Ac Induces Human Dental Pulp Stem Cell Osteo-/Odontoblastic Differentiation by Enhancing MAPK/ERK Pathway Activation.

作者信息

Li Changzhou, Xie Xinghuan, Liu Zhongjun, Yang Jianhua, Zuo Daming, Xu Shuaimei

机构信息

Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, China.

Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

出版信息

Stem Cells Int. 2021 Sep 23;2021:5560872. doi: 10.1155/2021/5560872. eCollection 2021.

DOI:10.1155/2021/5560872
PMID:34603453
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8483915/
Abstract

Dental pulp stem cells (DPSCs) must undergo odontoblastic differentiation in order to facilitate the process of dentin-pulp complex repair. Herein, we sought to explore the ability of Neu5Ac (one form of sialic acid) to influence DPSC osteo-/odontoblastic differentiation via modulating mitogen-activated protein kinase (MAPK) signaling. . DPSCs were isolated from human third permanent teeth and were grown Fluorescent microscopy was used to detect the existence of sialic acid on the DPSC membrane. Following the treatment of different concentrations of Neu5Ac and removing sialic acid from the cell surface by neuraminidase, the osteo-/odontoblastic differentiation of these cells was evaluated via mineralization, alkaline phosphatase, and assays. In addition, the expression of genes related to osteo-/odontoblastic differentiation and MAPK signaling at different stages of this differentiation process was analyzed in the presence or absence of Neu5Ac. . The existence of sialic acid on the DPSC membrane was confirmed by fluorescent microscopy, and the ability of osteo-/odontoblastic differentiation was decreased after removing sialic acid by neuraminidase. Treatment of DPSCs with Neu5Ac (0.1 mM or 1 mM) significantly enhanced their mineralization ability and alkaline phosphatase activity. The expression levels of DMP1, DSPP, BSP, and RUNX2 were also increased. Treatment of nude mice with ManNAc (the prerequisite form of Neu5Ac) also enhanced DPSC mineralization activity Furthermore, Neu5Ac treatment enhanced p-ERK expression in DPSCs, while ERK pathway inhibition disrupted the ability of Neu5Ac to enhance the osteo-/odontoblastic differentiation of these cells. . Neu5Ac can promote DPSC osteo-/odontoblastic differentiation through a process associated with the modulation of the ERK signaling pathway activity.

摘要

牙髓干细胞(DPSCs)必须经历成牙本质细胞分化,以促进牙本质-牙髓复合体的修复过程。在此,我们试图探索N-乙酰神经氨酸(Neu5Ac,唾液酸的一种形式)通过调节丝裂原活化蛋白激酶(MAPK)信号传导来影响DPSC向成骨/成牙本质细胞分化的能力。从人类第三恒磨牙中分离出DPSCs并进行培养。使用荧光显微镜检测DPSC膜上唾液酸的存在。在用不同浓度的Neu5Ac处理并通过神经氨酸酶从细胞表面去除唾液酸后,通过矿化、碱性磷酸酶和相关检测评估这些细胞的成骨/成牙本质细胞分化情况。此外,在有或没有Neu5Ac的情况下,分析了该分化过程不同阶段与成骨/成牙本质细胞分化和MAPK信号传导相关基因的表达。通过荧光显微镜证实了DPSC膜上唾液酸的存在,并且在通过神经氨酸酶去除唾液酸后,成骨/成牙本质细胞分化能力降低。用Neu5Ac(0.1 mM或1 mM)处理DPSCs显著增强了它们的矿化能力和碱性磷酸酶活性。DMP1、DSPP、BSP和RUNX2的表达水平也有所增加。用N-乙酰甘露糖胺(Neu5Ac的前体形式)处理裸鼠也增强了DPSC矿化活性。此外,Neu5Ac处理增强了DPSCs中p-ERK的表达,而ERK途径抑制则破坏了Neu5Ac增强这些细胞成骨/成牙本质细胞分化的能力。Neu5Ac可以通过与ERK信号通路活性调节相关的过程促进DPSC向成骨/成牙本质细胞分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/5d0c4a0e26b0/SCI2021-5560872.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/4c315bd67123/SCI2021-5560872.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/7ee6162b48fe/SCI2021-5560872.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/63a22bfadf85/SCI2021-5560872.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/d3172626938c/SCI2021-5560872.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/5d0c4a0e26b0/SCI2021-5560872.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/4c315bd67123/SCI2021-5560872.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/7ee6162b48fe/SCI2021-5560872.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/63a22bfadf85/SCI2021-5560872.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/d3172626938c/SCI2021-5560872.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f8a/8483915/5d0c4a0e26b0/SCI2021-5560872.005.jpg

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