Circadian rhythms regulate amelogenesis

Abstract

Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24h) intervals both at RNA and protein levels. This study also reveals that two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stage of amelogenesis might be under circadian control. Changes in clock genes expression patterns might result in significant alterations of enamel apposition and mineralization.

Circadian clock-mediated control of stem cell division and differentiation: beyond night and day

“…The observed circadian regulation of adult hippocampal neurogenesis (Bouchard-Cannon et al, 2013) could complement circadian regulation of dendritic spine formation and stabilization (Liston et al, 2013), allowing for more efficient reintegration of new neurons into the adult brain. A circadian clock is also present in tooth ameloblasts, where it controls antiphase rhythms of enamel matrix endocytosis and secretion, as well as ameloblast maturation (Lacruz et al, 2012;Zheng et al, 2013). Circadian oscillations in the release of hematopoietic stem cells (HSCs), coupled with antiphase circadian expression of the chemokine Cxcl12 and coordinated with GSK3β-dependent changes in HSC migratory properties (Lapid et al, 2013), could result in the coordinated release of HSCs and repopulation of the bone marrow stem cell niche (Méndez-Ferrer et al, 2009.…”

The tick tock of odontogenesis

“…Consistent with the above findings, our preliminary analysis of Per2 knock-out teeth show abnormal enamel matrix formation (unpublished). Our data also suggest that Kallikrein 4 ( Klk4 ), a key gene that regulates enamel maturation, might be under circadian control [31]. Taken together the above-discussed data, we postulate that enamel matrix production and maturation is closely controlled by selectively regulating some of enamel matrix proteins encoding genes.…”

“…Cross-striations delineate the amount of enamel deposited in a single day [29, 30]. Enamel cross-striations occur because of a circadian rhythm of ameloblast activity [27, 31]. Similar growth lines have been showed recently in mouse enamel as well [32].…”

“…It is possible that enamelin is not under circadian control. Of significance, amelogenin expression still oscillates under DD conditions, however in less extend and with a slight shift in peak times [31]. In vitro studies have also confirmed that amelogenin expression is modulated by clock genes [31, 34, 35] (Fig.…”

Measures of maturation in early fossil hominins: events at the first transition from australopiths to earlyHomo

“…This has become possible in a few cases by studying the incremental structure of tooth enamel and dentine [53][54][55][56]. The evidence that growth markings in enamel and dentine have a daily periodicity [57][58][59] has recently strengthened with new studies documenting the control of enamel matrix protein secretion by various clock-genes [60][61][62]. The ages at death cited in this study and the ages for defined stages of tooth development used here have all previously been published [34,35,[63][64][65][66][67][68][69][70] and are based on the daily incremental record preserved within fossil tooth enamel and dentine.…”