A study published in the journal Science Signaling found that excessive fluoride exposure can make changes to the calcium signaling, gene expression and mitochondrial function in enamel cells. This finding presents a novel explanation for the development of dental fluorosis, a condition caused by overexposure to fluoride during childhood.
Dental fluorosis causes discoloration of the teeth, usually accompanied by opaque white marks and poor mineralization. The condition is especially common when children up to nine years of age are exposed to excessive fluoride levels while their teeth are still forming, which increases their risk of developing tooth decay as well.
"Given how common dental fluorosis is and how poorly understood the cellular mechanisms responsible for this disease are, it is important to study this problem," said senior study author Rodrigo Lacruz.
In this study, researchers from the New York University (NYU) College of Dentistry aimed to look into the molecular bases of dental fluorosis. To do so, they analyzed the effects of fluoride exposure on enamel cells from rodents. The levels of fluoride used in the study were significantly higher than what could be found in drinking water and was consistent with the levels found in areas where people commonly develop fluorosis. Afterward, they assessed the impact of fluoride on the cell's calcium signaling, considering calcium's role in mineralizing tooth enamel. (Related: Toxic toothpaste ingredients that make us sick.)
From the results, the researchers observed that exposing rodent enamel cells to excessive levels of fluoride resulted in calcium dysregulation. This caused a notable decrease in calcium entering and being stored in the endoplasmic reticulum, a compartment within the cells that perform many functions, including the ability to store calcium. Furthermore, fluoride exposure also disrupted mitochondrial function, which affected the cell's energy production.
Lastly, the researchers used RNA sequencing to find that enamel cells exposed to fluoride exhibited an increased expression of genes encoding endoplasmic reticulum stress response proteins. It also increased the expression of the genes encoding mitochondrial proteins responsible for producing energy for cells.
According to the researchers, their findings present a very promising mechanistic view of how fluorosis develops. If cells needed to produce enamel – which is heavily calcified – while being exposed to fluoride, the cells would undergo continued stress in their capacity to handle calcium. This stress will be reflected in the enamel crystals and will affect mineralization.
To explore this further, the researchers repeated the same experiment, but used early-stage kidney cells from humans instead of enamel cells from rodents. However, they did not observe the same effects of fluoride exposure, suggesting that enamel cells are significantly different from the cells that form tissue in other parts of the body.
Lacruz says that the way enamel cells handle stress is vastly different from the coping mechanisms of kidney cells. Through their research, they are unveiling the mechanisms that highlight the uniqueness of enamel cells, as well as providing an explanation for why fluorosis is a bigger problem for the teeth than anywhere else.
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