New study offers mechanistic view of dental fluorosis occurrence
NEW YORK, U.S.: Fluoride can prevent dental caries by promoting mineralization and making tooth enamel more resistant to acid. However, a new study has found that exposing teeth to excessive fluoride alters calcium signaling, mitochondrial function and gene expression in the cells forming tooth enamel, which ultimately leads to dental fluorosis.
The Centers for Disease Control and Prevention (CDC) has called water fluoridation one of the greatest public health achievements of the 20th century for its role in reducing caries. Many countries add fluoride to the public water supply, and the U.S. Department of Health and Human Services currently recommends a level of 0.7 mg of fluoride per liter of water. However, while low levels of fluoride help strengthen and protect tooth enamel, too much fluoride can cause dental fluorosis. A recent survey by CDC found that roughly 25% of the U.S. population examined, which was aged 6–49 years old, showed some degree of dental fluorosis.
“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,” said senior author Dr. Rodrigo Lacruz, associate professor of basic science and craniofacial biology at the New York University College of Dentistry.
To investigate the molecular bases of dental fluorosis, the researchers analyzed the effects of exposing tooth enamel cells isolated from rodents to excessive levels of fluoride and assessed fluoride’s impact on calcium signaling within the cells.
The data showed that exposing enamel cells to fluoride led to a decrease in calcium entering and stored in the endoplasmic reticulum, the site of manufacture of proteins and lipids. In addition, fluoride disrupted the function of mitochondria and altered energy production. The researchers also noted that the enamel cells that were exposed to fluoride had a reduced expression of genes encoding endoplasmic reticulum stress response proteins and mitochondrial proteins, which are involved in producing the cell’s energy.
“This gives us a very promising mechanistic view of how fluorosis arises,” 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 mineralization.”
The researchers repeated the experiment using early-stage kidney cells from humans, but did not observe the same effects, suggesting that enamel cells differ from cells forming tissue in other parts of the body.
“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,” Lacruz noted. “Under the same circumstances, enamel cells react to coping with stress in vastly different ways than kidney cells. We are unraveling 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.”
According to CDC, 72.8% of the U.S. population on community water systems, that is, 201,565,162 people, had access to fluoridated water in 2016. In contrast, Dental Tribune International recently reported that only 6 million people in the UK are supplied with fluoridated water and that the Oral Health Foundation has urged the UK government to expand the areas of fluoridation across the country.
The study, titled “Fluoride exposure alters Ca2+ signaling and mitochondrial function in enamel cells,” was published on Feb. 18, 2020, in Science Signaling.