Researchers at NYC College of Dentistry have discovered that changes within enamel cells due to excessive fluoride can lead to fluorosis
The research, published in Science Signaling, reveals that exposing teeth to excessive fluoride alters calcium signalling, mitochondrial function, and gene expression in the cells forming tooth enamel – a novel explanation for how dental fluorosis, a condition caused by overexposure to fluoride during childhood, arises.
Preventing cavities with fluoride
Fluoride is a naturally occurring mineral that helps to prevent cavities by promoting mineralisation and making tooth enamel more resistant to acid.
Fluoride is added to drinking water around the world, the U.S. Department of Health and Human Services recommends a level of 0.7 parts per million, and all toothpaste backed by the American Dental Association’s Seal of Acceptance contain fluoride.
The Centers for Disease Control and Prevention (CDC) named water fluoridation one of ten great public health achievements of the 20th century for its role in reducing tooth decay.
While low levels of fluoride help strengthen and protect tooth enamel, too much fluoride can cause dental fluorosis which is a discolouration 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.
A survey by the CDC found that roughly 25% of the U.S. population examined (ages 6 to 49) show some degree of dental fluorosis.
Calcium signalling within the cells
Rodrigo Lacruz, PhD, associate professor of basic science and craniofacial biology at NYU College of Dentistry and the study’s senior author said: “The benefits of fluoride for oral health considerably outweigh the risks, 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 researcher team analysed the effects of exposing tooth enamel cells to fluoride levels on the higher end of what you would find in drinking water and consistent with what is found in areas where people commonly have fluorosis. They then assessed fluoride’s impact on calcium signalling within the cells, given calcium’s role in mineralising tooth enamel.
Disrupting the function of the mitochondria
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. Additionally, fluoride disrupted the function of mitochondria (the cells’ power generators), and therefore energy production was altered.
Finally, RNA sequencing queries the genomes of cells. The 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.
Fluoride puts the cells under stress
Lacruz explained: “This gives us a very promising mechanistic view of how fluorosis arises. 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.”
The researchers then repeated the experiment using early-stage kidney cells from humans, but they did not observe the same effects when the kidney cells were exposed to fluoride, suggesting that enamel cells are different from cells forming tissue in other parts of the body.
Lazcrus concluded: “You would think that if you expose the enamel cells and kidney cells to the same stressor, treating them with the same amount of fluoride for the same period of time, that you’d have more or less similar responses. But that was not the case,
“Under the same circumstances, enamel cells react to coping with stress in vastly different ways than kidney cells. We are unravelling a mechanism that highlights the uniqueness of enamel cells and explains why fluorosis is more of a problem in the teeth than anywhere else in the body.”