Regulation of pH During Amelogenesis

Abstract

During amelogenesis, extracellular matrix proteins interact with growing hydroxyapatite crystals to create one of the most architecturally complex biological tissues. The process of enamel formation is a unique biomineralizing system characterized first by an increase in crystallite length during the secretory phase of amelogenesis, followed by a vast increase in crystallite width and thickness in the later maturation phase when organic complexes are enzymatically removed. Crystal growth is modulated by changes in the pH of the enamel microenvironment that is critical for proper enamel biomineralization. Whereas the genetic bases for most abnormal enamel phenotypes (amelogenesis imperfecta) are generally associated with mutations to enamel matrix specific genes, mutations to genes involved in pH regulation may result in severely affected enamel structure, highlighting the importance of pH regulation for normal enamel development. This review summarizes the intra- and extracellular mechanisms employed by the enamel-forming cells, ameloblasts, to maintain pH homeostasis and, also, discusses the enamel phenotypes associated with disruptions to genes involved in pH regulation.

Fig. 1

Changing pH conditions impacting on enamel hydroxyapatite crystallite growth model. Two scenarios are shown: scenario A, where pH changes are dominated by nucleation, and scenario B, where gene expression initiates and controls pH changes in the enamel extracellular environment

Fig. 2

Simplified ameloblast bicarbonate transport model based on published data for NBCe1-B, AE2a, CFTR, CA2, and CA6. NBCe1-B is localized basolaterally and AE2a is expressed apically, while CA2 is intracellular and CA6 is secreted

Fig. 3

Scanning electron micrograph of molar teeth in Slc4a4-null mice. The three right mandibular molar teeth from the lateral view. Samples are 14-day-old wild-type (a) and Slc4a4-null (b) animals of the same litter. Scale bar: 0.5 mm