Exogenous transforming growth factor-β1 prevents the inflow of fluoride to ameleoblasts through regulation of voltage-gated chloride channels 5 and 7.

Abstract

Dental fluorosis is a global issue. Although there are multiple causes of dental fluorosis, the precise mechanism remains controversial. Previous studies have demonstrated that extracellular fluoride may promote an accumulation of fluoride ions in ameloblasts, which may induce oxidative and endoplasmic reticulum stresses, leading to dental fluorosis. However, the exact process by which fluoride ions enter cells has not been determined. In the present study, intracellular fluoride concentration was determined using a newly developed specific fluorescent probe called probe 1. Under high extracellular fluoride concentrations, the fluorescence intensity of the ameloblasts increased, however, exogenous transforming growth factor-β1 (TGF-β1) was able to inhibit the increase. Furthermore, changes in the expression of the voltage-gated chloride channels 5 and 7 (ClC5 and ClC-7), which are responsible for the transport of fluoride were investigated. The results indicated that fluoride reduced the expression of endogenous TGF-β1 and increased the expression of ClC-5 and ClC-7. Additionally, exogenous TGF-β1 reduced the expression of ClC-5 and ClC-7. The results of the present study indicate that exogenous TGF-β1 may prevent accumulation of fluoride in ameloblasts through the regulation of ClC-5 and ClC-7 under high extracellular fluoride concentrations.