Genetic defects lead to enamel malformations

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Mutations in a particular molecule lead to serious damage to the structure and mineral composition of tooth enamel in mice, according to a study by Swiss researchers.

Enamel is the hardest organic tissue that occurs in nature. It has a very complex structure, made up of minerals and enamel-specific proteins produced by tooth-exclusive cells called ameloblasts. However, as robust as tooth enamel is, it is still susceptible to damage: enamel defects are among the most common dental problems and result in pain-sensitive teeth and an increased risk of cavities.

A team of researchers from the Center for Dentistry at the University of Zurich has now identified for the first time a key gene network responsible for severe tooth enamel defects, and published their findings in iScience.

Using several genetically modified mouse models, the scientists analyzed the effects of the Adam10 molecule, which is closely linked to the Notch signaling pathway. This signaling pathway enables communication between adjacent cells, is essential for embryonic development and plays a critical role in the development of serious human pathologies such as stroke and cancer.

To study in detail the role of the Adam10/Notch signaling in tooth enamel formation and pathology and to analyze cellular and enamel structure modifications in teeth after gene mutation, the researchers used state-of-the-art genetic, molecular and imaging tools.

The scientists were able to show that there is a close relationship between reduced Adam10/Notch function and enamel defects.

“Mice carrying mutations of Adam10 have teeth with severe enamel defects,” said lead researcher Thimios Mitsiadis.

“Adam10 deletion causes disorganization of the ameloblasts, which subsequently leads to severe defects in both the structure and mineral composition of the enamel.

“The requirements for enamel repair and de novo formation are extremely complex, but new genetic and pharmaceutical tools targeting disrupted tooth enamel formation will allow us to significantly improve dental care in the future,” added Professor Mitsiadis.

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