title: Composition of mineralizing incisor enamel in cystic fibrosis transmembrane conductance regulator-deficient mice.
abstract: Formation of crystals in the enamel space releases protons that need to be buffered to sustain mineral accretion. We hypothesized that apical cystic fibrosis transmembrane conductance regulator (CFTR) in maturation ameloblasts transduces chloride into forming enamel as a critical step to secrete bicarbonates. We tested this by determining the calcium, chloride, and fluoride levels in developing enamel of Cftr-null mice by quantitative electron probe microanalysis. Maturation-stage enamel from Cftr-null mice contained less chloride and calcium than did wild-type enamel, was more acidic when stained with pH dyes ex vivo, and formed no fluorescent modulation bands after in vivo injection of the mice with calcein. To acidify the enamel further we exposed Cftr-null mice to fluoride in drinking water to stimulate proton release during formation of hypermineralized lines. In Cftr-deficient mice, fluoride further lowered enamel calcium without further reducing chloride levels. The data support the view that apical CFTR in maturation ameloblasts tranduces chloride into developing enamel as part of the machinery to buffer protons released during mineral accretion.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute, University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands.
authors.forename: Antonius L J J
authors.initials: AL
authors.lastname: Bronckers
authors.forename: Don M
authors.initials: DM
authors.lastname: Lyaruu
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.forename: Marcel J C
authors.initials: MJ
authors.lastname: Bijvelds
authors.forename: Theodore J M
authors.initials: TJ
authors.lastname: Bervoets
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zandieh-Doulabi
authors.forename: Juan F
authors.initials: JF
authors.lastname: Medina
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pamela K
authors.initials: PK
authors.lastname: DenBesten
mesh_terms: D000565:Ameloblasts / Q000378:metabolism; D000566:Amelogenesis / Q000502:physiology; D000818:Animals; D001639:Bicarbonates / Q000032:analysis; D002021:Buffers; D002118:Calcium / Q000032:analysis; D002327:Cariostatic Agents / Q000494:pharmacology; D002712:Chlorides / Q000032:analysis / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology*; D003743:Dental Enamel / Q000737:chemistry* / Q000187:drug effects; D004577:Electron Probe Microanalysis; D005452:Fluoresceins; D005456:Fluorescent Dyes; D005459:Fluorides / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D051379:Mice; D018181:Mice, Inbred CFTR; D014074:Tooth Calcification / Q000502:physiology*; D055114:X-Ray Microtomography / Q000379:methods
chemical_list: D001639:Bicarbonates; D002021:Buffers; D002327:Cariostatic Agents; D002712:Chlorides; D005452:Fluoresceins; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005459:Fluorides; D002118:Calcium; C007740:fluorexon
keywords: ameloblast modulation; anion exchanger-2; cystic fibrosis; enamel fluorosis; quantitative X-ray microanalysis