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J Dent Res. 2015 Oct;94(10):1471-7. doi: 10.1177/0022034515598144. Epub 2015 Jul 31.

Store-operated Ca2+ Entry Modulates the Expression of Enamel Genes.

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Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA.
Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA.
Department of Pathology, NYU School of Medicine, New York, NY, USA.
Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, NY, USA


Dental enamel formation is an intricate process tightly regulated by ameloblast cells. The correct spatiotemporal patterning of enamel matrix protein (EMP) expression is fundamental to orchestrate the formation of enamel crystals, which depend on a robust supply of Ca2+. In the extracellular milieu, Ca2+ -EMP interactions occur at different levels. Despite its recognized role in enamel development, the molecular machinery involved in Ca2+ homeostasis in ameloblasts remains poorly understood. A common mechanism for Ca2+ influx is store-operated Ca2+ entry (SOCE). We evaluated the possibility that Ca2+ influx in enamel cells might be mediated by SOCE and the Ca2+ release-activated Ca2+ (CRAC) channel, the prototypical SOCE channel. Using ameloblast-like LS8 cells, we demonstrate that these cells express Ca2+ -handling molecules and mediate Ca2+ influx through SOCE. As a rise in the cytosolic Ca2+ concentration is a versatile signal that can modulate gene expression, we assessed whether SOCE in enamel cells had any effect on the expression of EMPs. Our results demonstrate that stimulating LS8 cells or murine primary enamel organ cells with thapsigargin to activate SOCE leads to increased expression of Amelx, Ambn, Enam, Mmp20. This effect is reversed when cells are treated with a CRAC channel inhibitor. These data indicate that Ca2+ influx in LS8 cells and enamel organ cells is mediated by CRAC channels and that Ca2+ signals enhance the expression of EMPs. Ca2+ plays an important role not only in mineralizing dental enamel but also in regulating the expression of EMPs.


Fura-2; calcification; calcium channels; calcium signaling; dental enamel; physiology

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