Chronodentistry: the role &amp; potential of molecular clocks in oral medicine

Janjić, Klara; Agis, Hermann

doi:10.1186/s12903-019-0720-x

Cited by 14 publications

(22 citation statements)

References 96 publications

(99 reference statements)

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“…A chronotherapeutic approach to the use of CFA improves the clinical efficacy of NSPT. [ 44 45 ] It has been proven that pharmacokinetics and pharmacodynamics follow the circadian rhythms: optimizing the timing of medication administration taking into account that circadian fluctuations can increase the effectiveness of therapeutic measures. [ 45 46 ] Chronotherapy also reduces side effects and improves the overall drug safety.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of complex phytoadaptogens as an adjunct to non-surgical treatment of chronic periodontitis: A randomized clinical trial

Dzampaeva

Datieva

Esenova

et al. 2021

J Int Soc Prevent Communit Dent

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Section: Discussionmentioning

confidence: 99%

Efficacy of complex phytoadaptogens as an adjunct to non-surgical treatment of chronic periodontitis: A randomized clinical trial

Dzampaeva

Datieva

Esenova

et al. 2021

J Int Soc Prevent Communit Dent

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“…Subsequently, PER and CRY proteins multimerize with another core circadian regulator, casein kinase I δ in the cytoplasm and enter the nucleus to inhibit the activity of BMAL1/CLOCK complexes ( St. John et al, 2014 ). Both genes are involved in the circadian regulation of several physiological (e.g., bone metabolism) and pathological processes (e.g., development of cancer) ( Adeola et al, 2019 ; Janjiæ and Agis, 2019 ). In enamel, we have previously demonstrated that both Bmal1 and Per2 are robustly expressed by pre-ameloblast and differentiating ameloblasts in both human and mice embryonic teeth in addition to mice postnatal teeth ( Zheng et al, 2011 , 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Calcium Sets the Clock in Ameloblasts

et al. 2020

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Background: Stromal interaction molecule 1 (STIM1) is one of the main components of the store operated Ca 2+ entry (SOCE) signaling pathway. Individuals with mutated STIM1 present severely hypomineralized enamel characterized as amelogenesis imperfecta (AI) but the downstream molecular mechanisms involved remain unclear. Circadian clock signaling plays a key role in regulating the enamel thickness and mineralization, but the effects of STIM1-mediated AI on circadian clock are unknown. Objectives: The aim of this study is to examine the potential links between SOCE and the circadian clock during amelogenesis. Methods: We have generated mice with ameloblast-specific deletion of Stim1 (Stim1 fl/fl /Amelx-iCre +/+ , Stim1 cKO) and analyzed circadian gene expression profile in Stim1 cKO compared to control (Stim1 fl/fl /Amelx-iCre −/−) using ameloblast microdissection and RNA micro-array of 84 circadian genes. Expression level changes were validated by qRT-PCR and immunohistochemistry. Results: Stim1 deletion has resulted in significant upregulation of the core circadian activator gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocation 1 (Bmal1) and downregulation of the circadian inhibitor Period 2 (Per2). Our analyses also revealed that SOCE disruption results in dysregulation of two additional circadian regulators; p38α mitogen-activated protein kinase (MAPK14) and transforming growth factor-beta1 (TGF-β1). Both MAPK14 and TGF-β1 pathways are known to play major roles in enamel secretion and their dysregulation has been previously implicated in the development of AI phenotype. Conclusion: These data indicate that disruption of SOCE significantly affects the ameloblasts molecular circadian clock, suggesting that alteration of the circadian clock may be partly involved in the development of STIM1-mediated AI.

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“…Downregulation of hCRY2, hPER3 and hBMAL1 in tumoral tissues vs. their non-cancerous adjacent counterparts has been previously correlated with severity of tumor progression in a retrospective cohort of 40 head and neck squamous cell carcinoma patients (Hsu et al, 2012). A recent review article has further detailed the importance of circadian clock biology and its potential in various fields of dentistry (Janjic and Agis, 2019).…”

Section: Circadian Clock Oral Tissues Homeostasis and Head And Neckmentioning

confidence: 99%

Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective

Adeola

Papagerakis

2019

Front. Physiol.

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A vast majority of the pathophysiological and metabolic processes in humans are temporally controlled by a master circadian clock located centrally in the hypothalamic suprachiasmatic nucleus of the brain, as well as by specialized peripheral oscillators located in other body tissues. This circadian clock system generates a rhythmical diurnal transcriptional-translational cycle in clock genes and protein expression and activities regulating numerous downstream target genes. Clock genes as key regulators of physiological function and dysfunction of the circadian clock have been linked to various diseases and multiple morbidities. Emerging omics technologies permits largescale multi-dimensional investigations of the molecular landscape of a given disease and the comprehensive characterization of its underlying cellular components (e.g., proteins, genes, lipids, metabolites), their mechanism of actions, functional networks and regulatory systems. Ultimately, they can be used to better understand disease and interpatient heterogeneity, individual profile, identify personalized targetable key molecules and pathways, discover novel biomarkers and genetic alterations, which collectively can allow for a better patient stratification into clinically relevant subgroups to improve disease prediction and prevention, early diagnostic, clinical outcomes, therapeutic benefits, patient's quality of life and survival. The use of “omics” technologies has allowed for recent breakthroughs in several scientific domains, including in the field of circadian clock biology. Although studies have explored the role of clock genes using circadiOmics (which integrates circadian omics, such as genomics, transcriptomics, proteomics and metabolomics) in human disease, no such studies have investigated the implications of circadian disruption in oral, head and neck pathologies using multi-omics approaches and linking the omics data to patient-specific circadian profiles. There is a burgeoning body of evidence that circadian clock controls the development and homeostasis of oral and maxillofacial structures, such as salivary glands, teeth and oral epithelium. Hence, in the current era of precision medicine and dentistry and patient-centered health care, it is becoming evident that a multi-omics approach is needed to improve our understanding of the role of circadian clock-controlled key players in the regulation of head and neck pathologies. This review discusses current knowledge on the role of the circadian clock and the contribution of omics-based approaches toward a novel precision health era for diagnosing and treating head and neck pathologies, with an emphasis on oral, head and neck cancer and Sjögren's syndrome.

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Chronodentistry: the role & potential of molecular clocks in oral medicine

Cited by 14 publications

References 96 publications

Efficacy of complex phytoadaptogens as an adjunct to non-surgical treatment of chronic periodontitis: A randomized clinical trial

Efficacy of complex phytoadaptogens as an adjunct to non-surgical treatment of chronic periodontitis: A randomized clinical trial

Calcium Sets the Clock in Ameloblasts

Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective

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