title: Cystic fibrosis transmembrane conductance regulator (CFTR) regulates the production of osteoprotegerin (OPG) and prostaglandin (PG) E2 in human bone.
abstract: Bone loss is an important clinical issue in patients with cystic fibrosis (CF). Whether the cystic fibrosis transmembrane conductance regulator (CFTR) plays a direct role in bone cell function is yet unknown. In this study, we provide evidence that inhibition of CFTR-Cl(-) channel function results in a significant decrease of osteoprotegerin (OPG) secretion accompanied with a concomitant increase of prostaglandin (PG) E(2) secretion of primary human osteoblast cultures (n=5). Our data therefore suggest that in bone cells of CF patients, the loss of CFTR activity may result in an increased inflammation-driven bone resorption (through both the reduced OPG and increased PGE(2) production), and thus might contribute to the early bone loss reported in young children with CF.
authors.affiliation: Inserm UMR-S 926, IFR 53, Faculté de Médecine, Reims, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Le Heron
authors.forename: Christine
authors.initials: C
authors.lastname: Guillaume
authors.forename: Frédéric
authors.initials: F
authors.lastname: Velard
authors.forename: Julien
authors.initials: J
authors.lastname: Braux
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
authors.forename: Sandra
authors.initials: S
authors.lastname: Moriceau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Sermet-Gaudelus
authors.forename: Dominique
authors.initials: D
authors.lastname: Laurent-Maquin
authors.forename: Jacky
authors.initials: J
authors.lastname: Jacquot
mesh_terms: D000368:Aged; D001862:Bone Resorption / Q000209:etiology* / Q000503:physiopathology; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D053244:Osteoprotegerin / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C505032:CFTR protein, human; D053244:Osteoprotegerin; D012333:RNA, Messenger; C506030:TNFRSF11B protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015232:Dinoprostone