title: The F508del mutation in cystic fibrosis transmembrane conductance regulator gene impacts bone formation.
abstract: The F508del mutation in the cystic fibrosis transmembrane conductance regulator (Cftr) gene is believed to be an independent risk factor for cystic fibrosis-related bone disease. In this study, we evaluated the bone mineral density as well as the histomorphometric parameters of bone formation and bone mass in both F508del-Cftr homozygous mice (F508del Cftr(tm1Eur)) and Cftr(+/+) littermate controls at 6 (prepubertal), 10 (pubertal), and 14 (young adult) weeks of age in both sexes. The bone architecture of F508del Cftr(tm1Eur) and wild-type (WT) littermate mice was evaluated by bone densitometry, microcomputed tomography, and analysis of the dynamic parameters of bone formation. Serum levels of both insulin-like growth factor 1 and osteocalcin also were determined. Reduced bone mineral density, lower femoral bone mass, and altered trabecular bone architecture were observed in F508del Cftr(tm1Eur) mice compared with controls at 6, 10, and 14 weeks of age. A decrease in the bone formation rate in F508del Cftr(tm1Eur) mice was shown compared with control mice, independently of age and sex. In addition, we found lower insulin-like growth factor 1 levels in F508del Cftr(tm1Eur) mice compared with age-matched controls, whereas osteocalcin levels were normal. Severe osteopenia and altered bone architecture were found in young and mature adult F508del Cftr(tm1Eur) mice. Our findings show that the F508del mutation in CFTR impacts trabecular bone mass by reducing bone formation.
authors.affiliation: Equipe EA 4691, Biomateriaux et Inflammation en Site Osseux, SFR CAP-Santé, FED 4231, Université de Reims Champagne-Ardenne, Reims, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Le Henaff
authors.forename: Annelise
authors.initials: A
authors.lastname: Gimenez
authors.forename: Eric
authors.initials: E
authors.lastname: Haÿ
authors.forename: Caroline
authors.initials: C
authors.lastname: Marty
authors.forename: Pierre
authors.initials: P
authors.lastname: Marie
authors.forename: Jacky
authors.initials: J
authors.lastname: Jacquot
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001483:Base Sequence / Q000235:genetics*; D015519:Bone Density / Q000235:genetics; D001851:Bone Diseases, Metabolic / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000502:physiology; D005260:Female; D005269:Femur / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D010012:Osteogenesis / Q000235:genetics* / Q000502:physiology; D017384:Sequence Deletion
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator