p75NTR promotes tooth rhythmic mineralization via upregulation of BMAL1/CLOCK

作者全名："Xie, Bo; Yuan, Hongyan; Zou, Xuqiang; Lu, Mingjie; Zhang, Yixin; Xu, Dan; Peng, Xuelian; Wang, Di; Zhao, Manzhu; Wen, Xiujie"

作者地址："[Xie, Bo; Yuan, Hongyan; Zou, Xuqiang; Lu, Mingjie; Zhang, Yixin; Xu, Dan; Peng, Xuelian; Wen, Xiujie] Southwest Med Univ, Sch Stomatol, Dept Orthodont, Luzhou, Peoples R China; [Yuan, Hongyan; Wang, Di; Zhao, Manzhu] Chongqing Med Univ, Coll Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China"

通信作者："Wen, XJ (通讯作者)，Southwest Med Univ, Sch Stomatol, Dept Orthodont, Luzhou, Peoples R China.; Zhao, MZ (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001103084800001

JCR分区：Q1

影响因子：5.5

年份：2023

卷号：11

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：p75NTR; ectomesenchymal stem cells; circadian rhythm; mineralization; odontogenic differentiation; tooth development

摘要："The circadian clock plays a critical role in dentomaxillofacial development. Tooth biomineralization is characterized by the circadian clock; however, the mechanisms underlying the coordination of circadian rhythms with tooth development and biomineralization remain unclear. The p75 neurotrophin receptor (p75NTR) is a clock factor that regulates the oscillatory components of the circadian rhythm. This study aims to investigate the impact of p75NTR on the rhythmic mineralization of teeth and elucidate its underlying molecular mechanisms. We generated p75NTR knockout mice to examine the effects of p75NTR deficiency on tooth mineralization. Ectomesenchymal stem cells (EMSCs), derived from mouse tooth germs, were used for in vitro experiments. Results showed a reduction in tooth mineral density and daily mineralization rate in p75NTR knockout mice. Deletion of p75NTR decreased the expression of DMP1, DSPP, RUNX2, and ALP in tooth germ. Odontogenic differentiation and mineralization of EMSCs were activated by p75NTR. Histological results demonstrated predominant detection of p75NTR protein in odontoblasts and stratum intermedium cells during rapid formation phases of dental hard tissue. The mRNA expression of p75NTR exhibited circadian variations in tooth germs and EMSCs, consistent with the expression patterns of the core clock genes Bmal1 and Clock. The upregulation of BMAL1/CLOCK expression by p75NTR positively regulated the mineralization ability of EMSCs, whereas BMAL1 and CLOCK exerted a negative feedback regulation on p75NTR by inhibiting its promoter activity. Our findings suggest that p75NTR is necessary to maintain normal tooth biomineralization. Odontogenic differentiation and mineralization of EMSCs is regulated by the p75NTR-BMAL1/CLOCK signaling axis. These findings offer valuable insights into the associations between circadian rhythms, tooth development, and biomineralization."

基金机构：National Natural Science Foundation of China [cstc2020jcyj-msxmX0018]; Chongqing Natural Science Foundation of China

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Natural Science Foundation of China (81970906 and 82000997) and Chongqing Natural Science Foundation of China (cstc2020jcyj-msxmX0018)."