| First Author | Said R | Year | 2020 |
| Journal | Front Physiol | Volume | 11 |
| Pages | 920 | PubMed ID | 32848861 |
| Mgi Jnum | J:341837 | Mgi Id | MGI:6742046 |
| Doi | 10.3389/fphys.2020.00920 | Citation | Said R, et al. (2020) Calcium Sets the Clock in Ameloblasts. Front Physiol 11:920 |
| abstractText | 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 micro-dissection 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; p38alpha mitogen-activated protein kinase (MAPK14) and transforming growth factor-beta1 (TGF-beta1). Both MAPK14 and TGF-beta1 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. |
