title: The cystic fibrosis transmembrane conductance regulator (CFTR) is expressed in maturation stage ameloblasts, odontoblasts and bone cells.
abstract: Patients with cystic fibrosis (CF) have mild defects in dental enamel. The gene mutated in these patients is CFTR, a Cl(-) channel involved in transepithelial salt and water transport and bicarbonate secretion. We tested the hypothesis that Cftr channels are present and operating in the plasma membranes of mouse ameloblasts. Tissue sections of young mouse jaws and fetal human jaws were immunostained with various anti-Cftr antibodies. Specificity of the antibodies was validated in Cftr-deficient murine and human tissues. Immunostaining for Cftr was obtained in the apical plasma membranes of mouse maturation ameloblasts of both incisor and molar tooth germs. A granular intracellular immunostaining of variable intensity was also noted in bone cells and odontoblasts. In Cftr-deficient mice the incisors were chalky white and eroded much faster than in wild type mice. Histologically, only maturation ameloblasts of incisors were structurally affected in Cftr-deficient mice. Some antibody species gave also a positive cytosolic staining in Cftr-deficient cells. Transcripts of Cftr were found in maturation ameloblasts, odontoblasts and bone cells. Similar data were obtained in forming human dentin and bone. We conclude that Cftr protein locates in the apical plasma membranes of mouse maturation ameloblasts. In mouse incisors Cftr is critical for completion of enamel mineralization and conceivably functions as a regulator of pH during rapid crystal growth. Osteopenia found in CF patients as well as in Cftr-deficient mice is likely associated with defective Cftr operating in bone cells.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE , University of Amsterdam and VU University Amsterdam, The Netherlands. A.Bronckers@vumc.nl
authors.forename: Antonius
authors.initials: A
authors.lastname: Bronckers
authors.forename: Lida
authors.initials: L
authors.lastname: Kalogeraki
authors.forename: Huub J N
authors.initials: HJ
authors.lastname: Jorna
authors.forename: Martina
authors.initials: M
authors.lastname: Wilke
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Bervoets
authors.forename: Donacian M
authors.initials: DM
authors.lastname: Lyaruu
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zandieh-Doulabi
authors.forename: Pamela
authors.initials: P
authors.lastname: Denbesten
authors.forename: Hugo
authors.initials: H
authors.lastname: de Jonge
mesh_terms: D000565:Ameloblasts / Q000378:metabolism*; D000818:Animals; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D003743:Dental Enamel / Q000378:metabolism; D003804:Dentin / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007180:Incisor / Q000378:metabolism; D007568:Jaw / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009804:Odontoblasts / Q000378:metabolism*; D009805:Odontogenesis / Q000235:genetics; D010011:Osteocytes / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator