How too much fluoride causes defects in tooth enamel

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dental fluorosis
Photography: Ferli 123 RF

A US study has found that exposing teeth to excessive fluoride alters calcium signaling, mitochondrial function, and gene expression in the cells forming tooth enamel—a novel explanation for how dental fluorosis arises. 

The study, led by researchers at NYU College of Dentistry, is published in Science Signaling.

Fluoride is a naturally occurring mineral that helps to prevent cavities by promoting mineralisation and making tooth enamel more resistant to acid. 

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While low levels of fluoride help strengthen and protect tooth enamel, too much fluoride can cause dental fluorosis—a discoloration of teeth, usually with opaque white marks, lines, or mottled enamel and poor mineralisation. 

Dental fluorosis occurs when children between birth and around nine years of age are exposed to high levels fluoride during this critical window when their teeth are forming, and can actually increase their risk of tooth decay. 

“The benefits of fluoride for oral health considerably outweigh the risks,” Professor Rodrigo Lacruz said.

“But 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.”

To investigate the molecular bases of dental fluorosis, the researchers analysed the effects of exposing tooth enamel cells to fluoride—levels at the higher end of what is found in drinking water and consistent with what is found in areas where people commonly have fluorosis. They then assessed fluoride’s impact on calcium signaling within the cells, given calcium’s role in mineralising tooth enamel.

The researchers found that exposing enamel cells from rodents to fluoride resulted in calcium dysregulation, with decreases in calcium entering and stored in the endoplasmic reticulum, a compartment within cells with many functions, including storing calcium. 

In addition, fluoride disrupted the function of mitochondria (the cells’ power generators), and therefore energy production was altered. 

Finally, RNA sequencing revealed that, in enamel cells exposed to fluoride, there was an increased expression of genes encoding endoplasmic reticulum stress response proteins and those encoding mitochondrial proteins, which are involved in producing the cell’s energy.

“This gives us a very promising mechanistic view of how fluorosis arises,” Professor Lacruz said. 

“If your cells have to make enamel, which is heavily calcified, and due to exposure to too much fluoride the cells undergo continued stress in their capacity to handle calcium, that will be reflected in the enamel crystals as they are formed and will impact mineralisation.”

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