Functional expression of cystic fibrosis transmembrane conductance regulator in mouse chondrocytes

Abstract

1. Cystic fibrosis transmembrane conductance regulator (CFTR) is well known for its role in the cystic fibrosis (CF). Recent studies have shown that CF patients and CFTR-deficient mice exhibit a severe abnormal skeletal phenotype, indicating that CFTR may play a role in bone development and pathophysiological processes. However, it is not known whether CFTR has a direct or indirect effect on bone formation. The aim of the present study was to detect the expression and function of CFTR in mouse chondrocytes. 2. Reverse transcription-polymerase chain reaction, western blotting and immunofluorescence were used to characterize the expression of CFTR in primary isolated mouse chondrocytes. Expression of CFTR mRNA and protein was detectable in mouse chondrocytes. Importantly, whole-cell patch-clamp analysis demonstrated that CFTR in mouse chondrocytes is functional as a cAMP-dependent Cl(-) channel that is inhibited by CFTRinh-172. 3. Thus, the results of the present study demonstrate that functional CFTR is expressed in mouse chondrocytes, which offers essential evidence for the potential direct role of CFTR in physiological and pathological processes of bone.

Cystic Fibrosis Transmembrane Conductance Regulator in Sarcoplasmic Reticulum of Airway Smooth Muscle. Implications for Airway Contractility

“…CF disease manifestations are typically related to loss of CFTR function at the plasma membrane in epithelial cells. However, differing mechanisms of CFTR function in nonepithelial cells have been proposed, including intracellular vesicle acidification and SR calcium homeostasis in skeletal muscle (41)(42)(43)(44). The lack of localized plasma membrane CFTR staining in ASM is similar to that in other nonepithelial cells and suggests an intracellular function of CFTR in ASM.…”

Osteopenia in Cftr-deltaF508 mice

“…A second line, Cftr tm1Kth mice [10], express the mutated allele at a level of 25% relative to that of wild type mice expressing the wild type allele and this low level of expression in the intestine [10], but not other tissues including the lung, likely contributes to the lethal intestinal phenotype mice of this strain can develop. Although known to be expressed in bone [11,12] and in chondrocytes [13], the level of expression of Cftr in the bones of these ΔF508 Cftr mouse models has not been reported.…”

Inflammatory Diseases and Growth: Effects on the GH–IGF Axis and on Growth Plate

“…Animal models have shown that chondrocytes express functional CFTR [ 152 ], and cartilage abnormalities in tracheal ring structure have been reported in CF, both in humans and in animal models [ 153 , 154 ]. Both CFTR loss of function and local and systemic inflammation are hypothesised to be responsible for these changes, however, it is yet unclear whether cartilage abnormalities involve growth plate chondrocytes also, as these data are missing to date in the literature.…”