Odontoblasts, well-polarized columnar cells at the periphery of the dental pulp, originate from neural crest cells. They are primarily involved in dentin formation (dentinogenesis) as sites of the synthesis and secretion of collagenous and non-collagenous matrix proteins, and also participate in the directional transport of Ca
2+ from the circulation to the dentin-mineralizing front. Dentinogenesis is activated by: 1) pulpal patho-physiological events, such as intra-pulpal inflammatory responses, physiological or developmental processes, and 2) events at the dentin surface, such as various (mechanical/heat/cold) stimuli applied to the tooth surface. Therefore, the aim of this communication is to give an overview of the Ca2+-signaling system, which may have a major role in dentin formation in both physiological and pathological settings. Special attention will be given to discussion of the following: 1) sequential Ca
2+ signaling pathways from internal inositol 1,4,5-trisphosphate (IP
3) production
via the activation of phospholipase C-coupled receptors to the release of Ca
2+ from IP
3-sensitive Ca
2+ stores, 2) subsequent Ca
2+ influx
via store-operated Ca
2+ channels, and 3) the expression of transient receptor potential channels coupled with Na
+-Ca
2+ exchangers in odontoblasts.
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