Hair keratin mutations in tooth enamel increase dental decay risk

Tooth enamel is the hardest substance in the human body and has a unique combination of hardness and fracture toughness that protects teeth from dental caries, the most common chronic disease worldwide. In addition to a high mineral content, tooth enamel comprises organic material that is important for mechanical performance and influences the initiation and progression of caries; however, the protein composition of tooth enamel has not been fully characterized. Here, we determined that epithelial hair keratins, which are crucial for maintaining the integrity of the sheaths that support the hair shaft, are expressed in the enamel organ and are essential organic components of mature enamel. Using genetic and intraoral examination data from 386 children and 706 adults, we found that individuals harboring known hair disorder-associated polymorphisms in the gene encoding keratin 75 (KRT75), [KRT75.sup.A161T] and [KRT75.sup.E337K], are prone to increased dental caries. Analysis of teeth from individuals carrying the [KRT75.sup.A161T] variant revealed an altered enamel structure and a marked reduction of enamel hardness, suggesting that a functional keratin network is required for the mechanical stability of tooth enamel. Taken together, our results identify a genetic locus that influences enamel structure and establish a connection between hair disorders and susceptibility to dental caries.
Introduction Dental caries are initiated at the surface of the tooth by microorganisms metabolizing food residues and releasing acids that dissolve enamel minerals (1). Their development is influenced by nutrition, [...]