Changes within enamel cells point to mechanism by which excessive fluoride leads to fluorosis — ScienceDaily
When teeth are exposed to excessive fluoride, changes in calcium signaling, mitochondrial function, and gene expression in the cells that make up tooth enamel – a novel explanation of how dental fluorosis, a condition caused by overexposure to fluoride in childhood, occurs. The study, led by researchers from the NYU College of Dentistry, was published in Science Signaling.
Fluoride is a naturally occurring mineral that helps prevent cavities by promoting mineralization and making tooth enamel more acid resistant. It’s added to drinking water around the world – the US Department of Health recommends a level of 0.7 ppm – and all toothpastes with the American Dental Association seal of approval contain fluoride. The Centers for Disease Control and Prevention (CDC) cited water fluoridation as one of ten great public health achievements of the 20th century as it helps reduce tooth decay.
While low fluoride levels help strengthen and protect tooth enamel, too much fluoride can cause dental fluorosis – a discoloration of teeth, usually with opaque white spots, lines, or blotchy enamel and poor mineralization. Dental fluorosis occurs when children are exposed to high levels of fluoride between birth and around nine years of age during this critical window in which their teeth are forming, and it can actually increase the risk of tooth decay. A survey by the CDC found that around 25 percent of the US population (6 to 49 years old) studied had some degree of dental fluorosis.
“The oral health benefits of fluoride greatly outweigh the risks. However, given the prevalence of dental fluorosis and poor understanding of the cellular mechanisms responsible for this disease, it is important to investigate this problem,” said Dr. Rodrigo Lacruz, associate professor of basic research and craniofacial biology at NYU College of Dentistry and lead author on the study.
To examine the molecular basis of dental fluorosis, researchers analyzed the effects of exposure of enamel cells to fluoride – at the upper end of what you would find in drinking water and in line with what is found in areas where people are often suffer from fluorosis. They then assessed the influence of fluoride on the calcium signals in the cells, since calcium plays a role in the mineralization of tooth enamel.
The researchers found that exposure of rodent enamel cells to fluoride resulted in calcium dysregulation, with the decrease in calcium entering and becoming stored in the endoplasmic reticulum, a compartment within cells that has many functions including storing calcium. In addition, fluoride disrupted the function of the mitochondria (the cells’ electricity producers), and therefore the production of energy was changed. Finally, RNA sequencing – which queries the genome of cells – revealed that enamel cells exposed to fluoride had increased expression of genes coding for endoplasmic reticulum stress response proteins and genes coding for mitochondrial proteins Code that are involved in the cells’ production of energy.
“This gives us a promising mechanistic view of how fluorosis develops,” said Lacruz. “If your cells are forced to produce highly calcified enamel, and the cells are still able to deal heavily with calcium from exposure to too much fluoride, that will be reflected in the enamel crystals as they are formed and affect mineralization.”
The researchers then repeated the experiment with early-stage human kidney cells, but did not observe the same effects when the kidney cells were exposed to fluoride – suggesting that enamel cells are different from cells that make up tissues in other parts of the body.
“You’d think if you put the enamel cells and kidney cells under the same stressor – by treating them with the same amount of fluoride for the same amount of time – you’d have more or less similar reactions. But it wasn’t,” Lacruz said. “Under the same circumstances, enamel cells respond to stress management in a very different way than kidney cells. We are deciphering a mechanism that highlights the uniqueness of enamel cells and explains why fluorosis is a bigger problem in teeth than anywhere else in the world.” Body.”
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