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Composition of mineralizing incisor enamel in cystic fibrosis transmembrane conductance regulator‐deficient mice
Authors:Antonius LJJ Bronckers  Don M Lyaruu  Jing Guo  Marcel JC Bijvelds  Theodore JM Bervoets  Behrouz Zandieh‐Doulabi  Juan F Medina  Zhu Li  Yan Zhang  Pamela K DenBesten
Institution:1. Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute, University of Amsterdam and VU University Amsterdam, Amsterdam, the Netherlands;2. Department of Gastroenterology & Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands;3. Division of Gene Therapy and Hepatology, School of Medicine/CIMA, University of Navarra, and Ciberehd, Pamplona, Spain;4. Department of Oral and Craniofacial Sciences, School of Dentistry, University of California in San Francisco, San Francisco, CA, USA
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.
Keywords:anion exchanger‐2  ameloblast modulation  cystic fibrosis  enamel fluorosis  quantitative X‐ray microanalysis
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