PMID: 24529904

Le Henaff C, Hay E, Velard F, Marty C, Tabary O, Marie PJ, Jacquot JP
Enhanced F508del-CFTR channel activity ameliorates bone pathology in murine cystic fibrosis.
Am J Pathol. 2014 Apr;184(4):1132-41. doi: 10.1016/j.ajpath.2013.12.027. Epub 2014 Feb 11., [PubMed]
Sentences
No. Mutations Sentence Comment
13 ABCC7 p.Gly542*
X
ABCC7 p.Gly542* 24529904:13:1625
status: NEW
view ABCC7 p.Gly542* details
 (Am J Pathol 2014, 184: 1132e1141; http://dx.doi.org/10.1016/j.ajpath.2013.12.027) Cystic fibrosis (CF), which is caused by mutations of the CF transmembrane conductance regulator (CFTR), is characterized by multiorgan pathology that begins early in life.1e4 Brittle bones have been reported in children, adolescents, and adults with CF, independently of sex and age; this has been termed CF-related bone disease.5e8 Bone fragility may exclude patients from candidacy for lung transplantation, which imposes limitations on the best therapeutic option for these patients at the advanced stages of the disease.9 Clinical data have suggested a multifactorial etiology of CF-related skeletal deficits, including vitamin K and D insufficiency, calcium malabsorption, malnutrition and pancreatic insufficiency, delayed puberty, sex steroid deficiency, pulmonary infection/systemic inflammation, and frequent glucocorticoid therapy.10e13 Whether Cftr gene dysfunction plays a direct role in bone metabolism remains to be elucidated; however, this has been hypothesized on the basis of animal studies with the Cftr-null14,15 and F508del-Cftr mouse models.16,17 We previously reported that CF mice homozygous for the F508del-CFTR mutation develop a severe osteopenic phenotype in both sexes.16 In humans, the expression of CFTR protein has been identified in bone cells.18 We recently discovered defective CFTR-mediated Cl channel activity and a severe deficit of the release of osteoprotegerin (a key regulator in bone turnover) in primary osteoblasts (cells that form bone) obtained from a 25-year-old man with CF with the F508del/G542X mutation in CFTR.19 These data raise the hypothesis that the mutation in the Cftr gene may play a role in CF-related skeletal disease. Login to comment