Cystic fibrosis transmembrane conductance regulator (CFTR) regulates the production of osteoprotegerin (OPG) and prostaglandin (PG) E2 in human bone.
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.
Le Heron
Louis
L
Inserm UMR-S 926, IFR 53, Faculté de Médecine, Reims, France.
Guillaume
Christine
C
Velard
Frédéric
F
Braux
Julien
J
Touqui
Lhousseine
L
Moriceau
Sandra
S
Sermet-Gaudelus
Isabelle
I
Laurent-Maquin
Dominique
D
Jacquot
Jacky
J
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
C505032:CFTR protein, human; D053244:Osteoprotegerin; D012333:RNA, Messenger; C506030:TNFRSF11B protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015232:Dinoprostone