Abstract
Dental enamel, the final product of amelogenesis, is a highly mineralized bioceramic that becomes acellular and non-regenerating after tooth eruption. This paper reviews literature that explores inorganic phosphate (Pi) transport during the process of enamel formation or amelogenesis. Evidence from transcriptomics, immunolocalization, and physiology implicates ameloblast-specific sodium-dependent Pi uptake by type III sodium-phosphate cotransporters SLC20A1 (PiT1) and SLC20A2 (PiT2), and by type IIb sodium-phosphate cotransporter SLC34A2 (NaPi-IIb) with stage-specific basal (proximal) or apical (distal) enrichment, and pH-dependent expression. Controlled Pi efflux to the enamel space has been partly attributed to xenotropic and polytropic retrovirus receptor (XPR1) mediated Pi export during maturation-stage amelogenesis. These amelogenesis-specific Pi fluxes operate within a polarized cellular framework in which Ca(2+) delivery and extrusion, together with bicarbonate-based buffering regulated by cystic fibrosis transmembrane conductance regulator (CFTR), Solute carrier family 26 (SLC26) exchangers, anion exchanger 2 (AE2), and electrogenic sodium bicarbonate cotransporter 1 (NBCe1), at-least partially contribute to cellular Pi activity, and neutralize protons generated as the extracellular hydroxyapatite-based enamel matures. Disruption of phosphate handling reduces crystal growth and final mineral content of enamel, and produces hypomineralized or hypomature enamel with opacities, post-eruptive breakdown, and greater caries susceptibility. This review integrates multi-modal findings to appraise established features of ameloblast Pi handling, define constraints imposed by pH control and Ca(2+) transport, and identify gaps in ion transporter topology and trafficking dynamics.