A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development

Objective: Tooth morphogenesis and the formation of hard tissues have been reported to be closely related to circadian rhythms. This study investigates the spatiotemporal expression and relationship of p75NTR with core clock genes, mineralization-related or odontogenesis-related genes, and aims to d...

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Main Authors: Hongyan Yuan, Bo Xie, Xia Yu, Cheng Lin, Meng Li, Yixin Zhang, Xuqiang Zou, Mingjie Lu, Manzhu Zhao, Xiujie Wen
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-09-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2022.981311/full
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author Hongyan Yuan
Bo Xie
Xia Yu
Cheng Lin
Meng Li
Yixin Zhang
Xuqiang Zou
Mingjie Lu
Manzhu Zhao
Xiujie Wen
author_facet Hongyan Yuan
Bo Xie
Xia Yu
Cheng Lin
Meng Li
Yixin Zhang
Xuqiang Zou
Mingjie Lu
Manzhu Zhao
Xiujie Wen
author_sort Hongyan Yuan
collection DOAJ
description Objective: Tooth morphogenesis and the formation of hard tissues have been reported to be closely related to circadian rhythms. This study investigates the spatiotemporal expression and relationship of p75NTR with core clock genes, mineralization-related or odontogenesis-related genes, and aims to derive the potential role of p75NTR in regulating circadian rhythm and incrementality growth line formation during tooth development.Materials and methods: The dynamic morphology of the rat dental germ was observed at seven stages (E14.5 d, E16.5 d, E18.5 d, P.N. 4 d, P.N. 7 d, P.N. 10 d, and P.N. 15 d). Next, the expressions of p75NTR and other target factors were traced. The ectomesenchymal stem cells (EMSCs) were isolated from the E18.5d rat dental germs and synchronized using 50% of fetal bovine serum. Then, they were cultured in light/light (L.L.), dark/dark (D.D.), and light/dark (L.D.) conditions for 48 h. The total RNA was collected every 4 h, and the circadian rhythm dynamics of target factors were observed. To reveal the mechanism further, p75NTR was down-regulated in p75NTRExIII−/− mice and up-regulated in immortalized mouse dental apical papilla progenitor cells. The change tendencies of other target factors were also detected.Results: The clock genes Bmal1, Clock, Per1, and Per2 were all expressed in tooth germs before the formation of dental hard tissues and demonstrated a regular oscillating expression pattern in EMSCs from dental germs. Their expression was affected by the L.D. stimulus, and most of them were promoted by D.D. conditions. p75NTR presented a similar expression pattern and a positive or negative relationship with most clock genes, mineralization-related and odontogenesis-related factors, such as brain and muscle ARNT-like protein-1 (Bmal1), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), MSH-like 1 (MSX1), dentin matrix acidic phosphoprotein 1 (Dmp1), and dentin sialophosphoprotein (Dspp). Moreover, the arrangement, morphology, and even boundary in pre-odontoblast/pre-ameloblast layers were disordered in the p75NTRExIII−/− mice.Conclusion: Circadian rhythm was found to affect tooth development. p75NTR might play a crucial role in regulating clock genes in the mineralization and formation of the dental hard tissues. p75NTR is actively involved in the odontoblast-ameloblast junction and cell polarity establishment during tooth morphogenesis.
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spelling doaj.art-9749ba27f1b344969125c2d6f193aa932022-12-22T03:47:57ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-09-011310.3389/fphys.2022.981311981311A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth developmentHongyan Yuan0Bo Xie1Xia Yu2Cheng Lin3Meng Li4Yixin Zhang5Xuqiang Zou6Mingjie Lu7Manzhu Zhao8Xiujie Wen9Department of Orthodontics, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Orthodontics, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Orthodontics, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Oral Maxillofacial Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, ChinaChongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, College of Stomatology, Chongqing Medical University, Chongqing, ChinaDepartment of Orthodontics, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Orthodontics, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, ChinaDepartment of Orthodontics, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, ChinaChongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, College of Stomatology, Chongqing Medical University, Chongqing, ChinaDepartment of Orthodontics, The Affiliated Stomatology Hospital of Southwest Medical University, Luzhou, ChinaObjective: Tooth morphogenesis and the formation of hard tissues have been reported to be closely related to circadian rhythms. This study investigates the spatiotemporal expression and relationship of p75NTR with core clock genes, mineralization-related or odontogenesis-related genes, and aims to derive the potential role of p75NTR in regulating circadian rhythm and incrementality growth line formation during tooth development.Materials and methods: The dynamic morphology of the rat dental germ was observed at seven stages (E14.5 d, E16.5 d, E18.5 d, P.N. 4 d, P.N. 7 d, P.N. 10 d, and P.N. 15 d). Next, the expressions of p75NTR and other target factors were traced. The ectomesenchymal stem cells (EMSCs) were isolated from the E18.5d rat dental germs and synchronized using 50% of fetal bovine serum. Then, they were cultured in light/light (L.L.), dark/dark (D.D.), and light/dark (L.D.) conditions for 48 h. The total RNA was collected every 4 h, and the circadian rhythm dynamics of target factors were observed. To reveal the mechanism further, p75NTR was down-regulated in p75NTRExIII−/− mice and up-regulated in immortalized mouse dental apical papilla progenitor cells. The change tendencies of other target factors were also detected.Results: The clock genes Bmal1, Clock, Per1, and Per2 were all expressed in tooth germs before the formation of dental hard tissues and demonstrated a regular oscillating expression pattern in EMSCs from dental germs. Their expression was affected by the L.D. stimulus, and most of them were promoted by D.D. conditions. p75NTR presented a similar expression pattern and a positive or negative relationship with most clock genes, mineralization-related and odontogenesis-related factors, such as brain and muscle ARNT-like protein-1 (Bmal1), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), MSH-like 1 (MSX1), dentin matrix acidic phosphoprotein 1 (Dmp1), and dentin sialophosphoprotein (Dspp). Moreover, the arrangement, morphology, and even boundary in pre-odontoblast/pre-ameloblast layers were disordered in the p75NTRExIII−/− mice.Conclusion: Circadian rhythm was found to affect tooth development. p75NTR might play a crucial role in regulating clock genes in the mineralization and formation of the dental hard tissues. p75NTR is actively involved in the odontoblast-ameloblast junction and cell polarity establishment during tooth morphogenesis.https://www.frontiersin.org/articles/10.3389/fphys.2022.981311/fullp75 neurotrophin receptorcircadian rhythmmineralizationcell polaritytooth development
spellingShingle Hongyan Yuan
Bo Xie
Xia Yu
Cheng Lin
Meng Li
Yixin Zhang
Xuqiang Zou
Mingjie Lu
Manzhu Zhao
Xiujie Wen
A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development
Frontiers in Physiology
p75 neurotrophin receptor
circadian rhythm
mineralization
cell polarity
tooth development
title A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development
title_full A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development
title_fullStr A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development
title_full_unstemmed A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development
title_short A potential role of p75NTR in the regulation of circadian rhythm and incremental growth lines during tooth development
title_sort potential role of p75ntr in the regulation of circadian rhythm and incremental growth lines during tooth development
topic p75 neurotrophin receptor
circadian rhythm
mineralization
cell polarity
tooth development
url https://www.frontiersin.org/articles/10.3389/fphys.2022.981311/full
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