Buffering of protons released by mineral formation during amelogenesis in mice

Abstract

Regulation of pH by ameloblasts during amelogenesis is critical for enamel mineralization. We examined the effects of reduced bicarbonate secretion and the presence or absence of amelogenins on ameloblast modulation and enamel mineralization. To that end, the composition of fluorotic and non-fluorotic enamel of several different mouse mutants, including enamel of cystic fibrosis transmembrane conductance regulator-deficient (Cftr null), anion exchanger-2-deficient (Ae2a,b null), and amelogenin-deficient (Amelx null) mice, was determined by quantitative X-ray microanalysis. Correlation analysis was carried out to compare the effects of changes in the levels of sulfated-matrix (S) and chlorine (Cl; for bicarbonate secretion) on mineralization and modulation. The chloride (Cl ) levels in forming enamel determined the ability of ameloblasts to modulate, remove matrix, and mineralize enamel. In general, the lower the Cl content, the stronger the negative effects. In Amelx-null mice, modulation was essentially normal and the calcium content was reduced least. Retention of amelogenins in enamel of kallikrein-4-deficient (Klk4-null) mice resulted in decreased mineralization and reduced the length of the first acid modulation band without changing the total length of all acidic bands. These data suggest that buffering by bicarbonates is critical for modulation, matrix removal and enamel mineralization. Amelogenins also act as a buffer but are not critical for modulation.

Store-operated Ca2+ entry controls ameloblast cell function and enamel development

“…This might provide clues concerning potential signals that trigger the cyclic modulation of ameloblasts, which, to the best of our knowledge, has only been observed in this cell type. Rather than being triggered by the external environment of the cell, as has been suggested (38), our data support a scenario in which this cyclic modulation can be activated by changes in intracellular [Ca 2+ ]. A significant outcome of this study is that in the absence of dental tissues from patients with SOCE deficiency, the Stim1/2 K14cre mice are an important tool to investigate the effects of CRAC channel deficiency in 2+ stores does not result in appropriate activation of STIM1 and STIM2, and hence Ca 2+ entry via Orai1 is impaired, resulting in Ca 2+ -induced ER stress.…”

No Change in Bicarbonate Transport but Tight-Junction Formation Is Delayed by Fluoride in a Novel Ameloblast Model

“…The CO 2 / equilibrium is central to the proper regulation of extracellular pH by ameloblasts during enamel mineralization (Lacruz et al, 2010 , 2012 , 2013 ; Bronckers et al, 2016 ). A major finding in our previous work was that HAT-7 cells grown as a monolayer on Transwell membranes are capable of apical-to-basolateral secretion (Bori et al, 2016 ).…”

Enamel biomimetics—fiction or future of dentistry

“…14,15 The high ion concentrations and dramatic pH changes involved in initial amelogenesis pose a formidable hurdle in cell-based approaches toward tooth enamel regeneration. 16–18 And even though the synthesis of hydroxyapatite blocks may appear straight-forward from a manufacturing perspective, the faithful fabrication of true enamel with its parallel-aligned filigree apatite crystals and decussating prism bundles has rarely been accomplished so far. 19–23…”