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

Huang, Wushuang; Zheng, Xueqing; Yang, Mei; Li, Ruiqi; Song, Yaling

doi:10.1038/s41368-021-00123-7

Cited by 11 publications

(17 citation statements)

References 42 publications

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“…A similar oscillation was observed in p75NTR and Runx2 mRNA expression but not in Dlx1 mRNA expression, indicating that p75NTR and mineralizationrelated factor Runx2 might be involved in the circadian rhythm of tooth development. Previous studies support this finding that clock genes (Bmal1, Clock, Per1, and Per2) and two markers of ameloblast differentiation (amelogenin and kallikrein-related peptidase 4) have regular oscillations in ameloblasts (Zheng et al, 2013;Huang et al, 2021). Moreover, this oscillation was affected by L.D.…”

Section: Figurementioning

confidence: 54%

“…Previous studies reported the detection of clock genes in dental germs and depicted a regular oscillation expression pattern, indicating that biological clocks affect tooth development (Nirvani et al, 2017;Papakyrikos et al, 2020;Huang et al, 2021). The 48-h circadian rhythm dynamics in rat EMSCs showed that the clock genes Bmal1, Clock, and Per1 presented a regular oscillation in mRNA expression.…”

Section: Figurementioning

confidence: 86%

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

Yuan

Xie

et al. 2022

Front. Physiol.

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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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Section: Figurementioning

confidence: 54%

Section: Figurementioning

confidence: 86%

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

Yuan

Xie

et al. 2022

Front. Physiol.

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“…Mutations in KLK4 could cause nonsyndromic enamel malformations in humans and mice ( Lu et al, 2008 ). The expression of AMELX and PPARγ was decreased in Per2 knockdown ameloblast lineage cells, and overexpression of PPARγ partially reversed this phenomenon, Per2 regulates ameloblast differentiation mainly via the PPARγ/AKT1/β-catenin signaling axis ( Huang et al, 2021 ). Runx2 is involved in the whole process of tooth development, and Runx2 knockout mice are a representative congenital tooth agenesis model ( Chen et al, 2020 ).…”

Section: Circadian Rhythm/clock Genes Regulate Maxillofacial Embryoni...mentioning

confidence: 99%

Circadian clock—A promising scientific target in oral science

et al. 2022

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The oral and maxillofacial organs play vital roles in chewing, maintaining facial beauty, and speaking. Almost all physiological processes display circadian rhythms that are driven by the circadian clock, allowing organisms to adapt to the changing environment. In recent years, increasing evidence has shown that the circadian clock system participates in oral and maxillofacial physiological and pathological processes, such as jaw and tooth development, salivary gland function, craniofacial malformations, oral carcinoma and other diseases. However, the roles of the circadian clock in oral science have not yet been comprehensively reviewed. Therefore, This paper provides a systematic and integrated perspective on the function of the circadian clock in the fields of oral science, reviews recent advances in terms of the circadian clock in oral and maxillofacial development and disease, dialectically analyzes the importance of the circadian clock system and circadian rhythm to the activities of oral and maxillofacial tissues, and focuses on analyzing the mechanism of the circadian clock in the maintenance of oral health, affecting the common diseases of the oral and maxillofacial region and the process of oral-related systemic diseases, sums up the chronotherapy and preventive measures for oral-related diseases based on changes in tissue activity circadian rhythms, meanwhile, comes up with a new viewpoint to promote oral health and human health.

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“…Mechanistically, circadian rhythm alterations have been linked to the ß-catenin/WNT-signaling pathway. Indeed, circadian rhythm disrupted mice were demonstrated to exhibit both a decrease in expression of Bmal1 and β-catenin [ 23 ]. Bmal1, the major regulator of circadian activity, was shown to stimulate the WNT/β-catenin pathway by enhancing the transcription of β-catenin, decreasing the degradation of β-catenin [ 24 ], and downregulating Glycogen synthase kinase-3β (GSK-3β) activity [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway

et al. 2022

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We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.

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

Cited by 11 publications

References 42 publications

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

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

Circadian clock—A promising scientific target in oral science

Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway

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