Magnesium, pH regulation and modulation by mouse ameloblasts exposed to fluoride

Supraoptimal intake of fluoride (F) induces structural defects in forming enamel, dentin and bone and increases the risk of bone fractures. In comparison to bone and dentin is formation of enamel most sensitive to low levels of F and the degree of enamel fluorosis depends on the mouse strain. What molecular mechanism is responsible for these differences in sensitivity is unclear. Maturation ameloblasts transport bicarbonates into enamel in exchange for Cl- to buffer protons released by forming apatites. We proposed that F-enhanced mineral deposition releases excess of protons that will affect mineralization in forming enamel. In this study we tested the hypothesis that increased sensitivity to F is associated with a reduced capacity of ameloblasts to buffer acids. Quantified electron probe microanalysis showed that enamel of F-sensitive C57Bl mice contained the same levels of Cl- as enamel of F-resistant FVB mice. Enamel of C57Bl mice was less mineral dense, contained less Ca but more Mg and K. Ameloblast modulation was much more impaired than in FVB mice. In enamel of FVB mice the levels of Mg correlated negative with Ca (r=-0.57, p=0.01) and with the Ca/P molar ratio (r=-0.32, p=0.53). In moderate and high acidic enamel the correlations between Mg and Ca/P ratio were strong (r=-0.75, p=0.08) to very strong negative (r=-0.98, p=0.0020), respectively. Correlations in enamel between F and Ca were (weak) negative but between F and Ca/P very high positive (r=+0.95, p=0.003) in high acidic enamel and less positive (r=0.45, p=0.27) in moderate acidic fluorotic enamel (r=0.45, p=0.27). Similar correlations between Mg and Ca/P or F and Ca/P were found in dentin and bone of fluorotic and Cftr null mice. These data are consistent with the concept that Mg delays but F increases maturation of crystals particularly when enamel is acidic. The sensitivity of forming enamel to F likely is due to the sensitivity of pH cycling to acidification of enamel associated with F-induced release of protons.