title: Keratins as components of the enamel organic matrix.
abstract: Dental enamel is the hardest tissue in the human body, and although it starts as a tissue rich in proteins, by the time of eruption of the tooth in the oral cavity only a small fraction of the protein remains. While this organic matrix of enamel represents less than 1% by weight it plays essential roles in improving both toughness and resilience to chemical attacks. Despite the fact that the first studies of the enamel matrix began in the 19th century, its exact composition and mechanisms of its function remain poorly understood. It was proposed that keratin or a keratin-like primitive epithelial component exists in mature enamel, however due to the extreme insolubility of its organic matrix the presence of keratins there was never clearly established. We have recently identified expression of a number of hair keratins in ameloblasts, the enamel secreting cells, and demonstrated their incorporation into mature enamel. Mutation in epithelial hair keratin KRT75 leads to a skin condition called pseudofollicularis barbae. Carriers of this mutation have an altered enamel structure and mechanical properties. Importantly, these individuals have a much higher prevalence of caries. To the best of our knowledge, this is the first study showing a direct link between a mutation in a protein-coding region of a gene and increased caries rates. In this paper we present an overview of the evidence of keratin-like material in enamel that has accumulated over the last 150years. Furthermore, we propose potential mechanisms of action of KTR75 in enamel and highlight the clinical implications of the link between mutations in KRT75 and caries. Finally, we discuss the potential use of keratins for enamel repair.
authors.affiliation: Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Olivier
authors.initials: O
authors.lastname: Duverger
authors.affiliation: Department of Oral Biology, Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, United States; Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA, United States; McGowan Institute for Regenerative Medicine, Pittsburgh, PA, United States. Electronic address: ebeniash@pitt.edu.
authors.forename: Elia
authors.initials: E
authors.lastname: Beniash
authors.affiliation: Laboratory of Skin Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States. Electronic address: morasso@nih.gov.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Morasso
mesh_terms: D000818:Animals; D003731:Dental Caries / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism; D003743:Dental Enamel / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D006201:Hair Diseases / Q000150:complications / Q000235:genetics; D006801:Humans; D053564:Keratins, Hair-Specific / Q000235:genetics* / Q000378:metabolism*; D053531:Keratins, Type II / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D005499:Folliculitis
chemical_list: C502884:KRT75 protein, human; D053564:Keratins, Hair-Specific; D053531:Keratins, Type II
keywords: Caries; Enamel; Keratins; Organic matrix; Tooth