title: Nrf2 deficiency causes tooth decolourization due to iron transport disorder in enamel organ.
abstract: Rodents have brownish-yellow incisors whose colour represents their iron content. Iron is deposited into the mature enamel by ameloblasts that outline enamel surface of the teeth. Nrf2 is a basic region-leucine zipper type transcription factor that regulates expression of a range of cytoprotective genes in response to oxidative and xenobiotic stresses. We found that genetically engineered Nrf2-deficient mice show decolourization of the incisors. While incisors of wild-type mice were brownish yellow, incisors of Nrf2-deficient mice were greyish white in colour. Micro X-ray imaging analysis revealed that the iron content in Nrf2-deficient mouse incisors were significantly decreased compared to that of wild-type mice. We found that iron was aberrantly deposited in the papillary layer cells of enamel organ in Nrf2-deficient mouse, suggesting that the iron transport from blood vessels to ameloblasts was disturbed. We also found that ameloblasts of Nrf2-null mouse show degenerative atrophy at the late maturation stage, which gives rise to the loss of iron deposition to the surface of mature enamel. Our results thus demonstrate that the enamel organ of Nrf2-deficient mouse has a reduced iron transport capacity, which results in both the enamel cell degeneration and disturbance of iron deposition on to the enamel surface.
authors.affiliation: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Ken
authors.initials: K
authors.lastname: Itoh
authors.forename: Junya
authors.initials: J
authors.lastname: Uwayama
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shibata
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Tsuneyoshi
authors.initials: T
authors.lastname: Sano
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001692:Biological Transport; D004268:DNA-Binding Proteins / Q000235:genetics*; D003743:Dental Enamel / Q000378:metabolism* / Q000648:ultrastructure; D005293:Ferritins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007501:Iron / Q000378:metabolism*; D051379:Mice; D008855:Microscopy, Electron, Scanning; D051267:NF-E2-Related Factor 2; D014075:Tooth Discoloration / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D015534:Trans-Activators; D005293:Ferritins; D007501:Iron