Msx2通过调控细胞骨架及细胞间相互作用影响外釉上皮细胞分化  

Msx2 regulates differentiation of outer enamel epithelial cells by modulating cytoskeleton and cell-cell interactions

作　　者：于喆 季小禾 白靖琨 张丽辉 张娟娟 孙岩 陈丽梅 刘晓影 YU Zhe;JI Xiaohe;BAI Jingkun;ZHANG Lihui;ZHANG Juanjuan;SUN Yan;CHEN Limei;LIU Xiaoying(School of Bioscience and Technology,Weifang 261053,China;School of Stomatology,Shandong Second Medical University,Weifang 261053,China)

机构地区：[1]山东第二医科大学生命科学与技术学院,山东潍坊261053 [2]山东第二医科大学口腔医学院,山东潍坊261053

出　　处：《中国病理生理杂志》2025年第3期555-561,共7页Chinese Journal of Pathophysiology

基　　金：山东省自然科学基金资助项目(No.ZR2021MH397);山东省中医药科技项目(No.2021Z035)。

摘　　要：目的:探究肌节同源框2(muscle segment homeobox 2,Msx2)调控外釉上皮细胞分化的机制。方法:通过制备石蜡组织切片并进行苏木精-伊红(hematoxylin-eosin,HE)染色,在组织形态水平分析Msx2缺失对外釉上皮细胞分化状态的影响;在超显微结构水平分析细胞结构的变化,寻找介导细胞分化的中间环节。通过转录组测序分析,在分子水平进行验证,初步探索现象背后的分子机制。结果:组织学分析发现Msx2基因敲除引发外釉上皮细胞发生鳞状上皮化增生,超微结构显示细胞黏附增强和细胞骨架动态重构。Msx2作为转录抑制因子,其表达缺失引发整合素β2(integrinβ2,Itgβ2)、ItgαM、Itgα4、Rac家族小GTP酶2(Rac family small GTPase 2,Rac2)、Rac/Cdc42鸟嘌呤核苷酸交换因子6(Rac/Cdc42 guanine nucleotide exchange factor 6,Arhgef6)和蛋白酪氨酸磷酸酶受体C型(protein tyrosine phosphatase receptor type C,Ptprc)的mRNA表达水平显著升高(P<0.05或P<0.01)。结论:Msx2通过Rho GTP酶信号通路调控细胞骨架结构及细胞间相互作用,进而影响外釉上皮细胞的分化状态。本研究初步揭示了Msx2调控外釉上皮细胞分化的机制,为临床上牙釉质疾病的预防和治疗提供理论依据。AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P<0.05 or P<0.01)in the mRNA expression levels of integrinβ2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enamel-related clinical dental diseases.

关 键 词：Msx2蛋白 外釉上皮细胞 细胞分化 细胞黏附 细胞骨架 

分 类 号：Q291[生物学—细胞生物学] R78[医药卫生—口腔医学] R363.2[医药卫生—临床医学]