Calcium Sets the Clock in Ameloblasts

• Published in: Frontiers in physiology Vol. 11; p. 920
• Main Authors: Said, Raed, Lobanova, Liubov, Papagerakis, Silvana, Papagerakis, Petros
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 31.07.2020
• Subjects: ameloblast; calcium; circadian clock; enamel; Physiology; STIM1; store operated Ca2+ channels; calcium; STIM1; enamel; ameloblast; circadian clock; amelogenesis; amelogenesis imperfecta; store operated Ca2+ channels
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2020.00920

Stromal interaction molecule 1 ( ) is one of the main components of the store operated Ca entry (SOCE) signaling pathway. Individuals with mutated 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 -mediated AI on circadian clock are unknown. The aim of this study is to examine the potential links between SOCE and the circadian clock during amelogenesis. We have generated mice with ameloblast-specific deletion of ( /Amelx-iCre , cKO) and analyzed circadian gene expression profile in compared to control ( /Amelx-iCre ) using ameloblast micro-dissection and RNA micro-array of 84 circadian genes. Expression level changes were validated by qRT-PCR and immunohistochemistry. deletion has resulted in significant upregulation of the core circadian activator gene Brain and Muscle Aryl Hydrocarbon Receptor Nuclear Translocation 1 ( ) and downregulation of the circadian inhibitor Period 2 ( ). 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. 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 -mediated AI.