Sulphur dioxide and fluoride co-exposure induce incisor hypomineralization and amelogenin upregulation via YAP/RUNX2 signaling pathway

Sulphur dioxide (SO2) and fluoride are among the most common environmental pollutants affecting human health, and both co-exist in areas predominantly consuming coal. It is vital to analyse the combined toxicity of SO2 and fluoride, and their effects on health and the underlying mechanisms of their co-exposure have not yet been adequately assessed. In the present study, we used ICR mice and LS8 cells to investigate the toxicity of SO2 and fluoride exposure to the enamel, alone or in combination. Factorial design analysis was used to reveal the combined toxicity in vitro and in vivo. Co-exposure to SO2 and fluoride exacerbated enamel injury, resulting in more severe hypomineralization of incisor, and enamel structure disorders in mice, and could induce the accumulation of protein residue in the matrix of the enamel. Amelogenin expression was increased upon exposure to SO2 and fluoride, but enamel matrix proteases were not affected. Consistent with our in vivo results, co-exposure of SO2 and fluoride aggravated amelogenin expression in LS8 cells, and increased the YAP and RUNX2 levels. Co-exposure to SO2 and fluoride resulted in greater toxicity than individual exposure, both in vitro and in vivo, indicating that residents of areas exposed to SO2 and fluoride may have an increased risk of developing enamel damage.

Automated summary

Sulphur dioxide (SO2) and fluoride are common environmental pollutants that have a significant impact on human health, particularly in areas where coal consumption is high. The combined toxicity of SO2 and fluoride, as well as their effects on health and underlying mechanisms, have not been adequately assessed. This study used mice and cells to investigate the toxicity of SO2 and fluoride exposure on enamel. The findings suggest that co-exposure to SO2 and fluoride exacerbates enamel injury, resulting in more severe hypomineralization and structural disorders. These effects were also observed at the cellular level. The study concludes that residents in areas exposed to both SO2 and fluoride may have an increased risk of enamel damage.