Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment

作者全名："Wang, Min; Liu, Min; Zheng, Jiawen; Xiong, Li; Wang, Ping"

作者地址："[Wang, Min; Liu, Min; Zheng, Jiawen; Wang, Ping] Chongqing Med Univ, Dept Stomatol, Affiliated Hosp 1, Youyi Rd 1, Chongqing 400016, Peoples R China; [Xiong, Li] Chongqing Med Univ, Dept Pharm, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Wang, P (通讯作者)，Chongqing Med Univ, Dept Stomatol, Affiliated Hosp 1, Youyi Rd 1, Chongqing 400016, Peoples R China."

来源：OPEN MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000964793000001

JCR分区：Q2

影响因子：1.7

年份：2023

卷号：18

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Exendin-4; osteogenic differentiation; PDLSCs; high glucose; MAPK signaling; WNT signaling

摘要："Diabetes mellitus (DM) increases the destruction of periodontal tissue and impairs osteogenesis differentiation. Exendin-4 (Ex-4), a glucagon-like peptide-1 (GLP-1) analogue, can be used for treating DM and promotes bone regeneration. The aim of this study was to explore the effect and mechanism of Ex-4 on improving the osteogenesis of periodontal ligament stem cells (PDLSCs) in a high glucose environment. Alkaline phosphatase staining and alizarin red staining were used to detect the osteogenic differentiation of PDLSCs. The results showed that 10 nM Ex-4 could reduce the osteogenesis inhibition of PDLSCs induced by high glucose. RT-PCR and western blot results showed that Ex-4 increased the osteogenesis-related gene expression of ALP, Runx2, and Osx, and upregulated the phosphorylation of P38, JNK, and ERK1/2; the peak effect was observed in the range 0.5-1.0 h. Mitogen-activated protein kinase (MAPK) inhibitors PD98059, SB203580, and SP600125 blocked the effects of Ex-4 on MAPK activation and decreased the expression of ALP, Runx2, and Osx in PDLSCs. Moreover, after Ex-4 treatment, the total b-catenin, p-GSK3b, LEF, and Runx2 protein levels increased under normal or high glucose environments. In conclusion, our results indicated that Ex-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of PDLSCs in a high glucose environment."

基金机构：Basic Research and Frontier Exploration Project of Chongqing Municipal Science and Technology Commission [cstc2018jcyjAX0829]

基金资助正文：This research was supported by the Basic Research and Frontier Exploration Project of Chongqing Municipal Science and Technology Commission (cstc2018jcyjAX0829).