PER2-mediated ameloblast differentiation via PPARγ/AKT1/β-catenin axis  

作　　者：Wushuang Huang Xueqing Zheng Mei Yang Ruiqi Li Yaling Song 

机构地区：[1]The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST)and Key Laboratory of Oral Biomedicine Ministry of Education,School and Hospital of Stomatology,Wuhan University,Wuhan,China

出　　处：《International Journal of Oral Science》2021年第2期190-199,共10页国际口腔科学杂志（英文版）

基　　金：the National Natural Science Foundation of China,grant number No.81670976.

摘　　要：Circadian rhythm is involved in the development and diseases of many tissues.However,as an essential environmental regulating factor,its effect on amelogenesis has not been fully elucidated.The present study aims to investigate the correlation between circadian rhythm and ameloblast differentiation and to explore the mechanism by which circadian genes regulate ameloblast differentiation.Circadian disruption models were constructed in mice for in vivo experiments.An ameloblast-lineage cell(ALC)line was used for in vitro studies.As essential molecules of the circadian system,Bmal1 and Per2 exhibited circadian expression in ALCs.Circadian disruption mice showed reduced amelogenin(AMELX)expression and enamel matrix secretion and downregulated expression of BMAL1,PER2,PPARγ,phosphorylated AKT1 andβ-catenin,cytokeratin-14 and F-actin in ameloblasts.According to previous findings and our study,BMAL1 positively regulated PER2.Therefore,the present study focused on PER2-mediated ameloblast differentiation and enamel formation.Per2 knockdown decreased the expression of AMELX,PPARγ,phosphorylated AKT1 andβ-catenin,promoted nuclearβ-catenin accumulation,inhibited mineralization and altered the subcellular localization of E-cadherin in ALCs.Overexpression of PPARγpartially reversed the above results in Per2-knockdown ALCs.Furthermore,in in vivo experiments,the length of incisor eruption was significantly decreased in the circadian disturbance group compared to that in the control group,which was rescued by using a PPARγagonist in circadian disturbance mice.In conclusion,through regulation of the PPARγ/AKT1/β-catenin signalling axis,PER2 played roles in amelogenin expression,cell junctions and arrangement,enamel matrix secretion and mineralization during ameloblast differentiation,which exert effects on enamel formation.

关 键 词：PER2 inhibited AKT1 

分 类 号：R780.2[医药卫生—口腔医学]