Bone Cells Differentiation: How CFTR Mutations May Rule the Game of Stem Cells Commitment?

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2021 May 24

PMID 34026749

Citations 7

Authors

Claire Dumortier

Soula Danopoulos

Frdric Velard

Denise Al Alam

Affiliations

Soon will be listed here.

Abstract

Cystic fibrosis (CF)-related bone disease has emerged as a significant comorbidity of CF and is characterized by decreased bone formation and increased bone resorption. Both osteoblast and osteoclast differentiations are impacted by cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The defect of CFTR chloride channel or the loss of CFTRs ability to interact with other proteins affect several signaling pathways involved in stem cell differentiation and the commitment of these cells toward bone lineages. Specifically, TGF-, nuclear factor-kappa B (NF-B), PI3K/AKT, and MAPK/ERK signaling are disturbed by CFTR mutations, thus perturbing stem cell differentiation. High inflammation in patients changes myeloid lineage secretion, affecting both myeloid and mesenchymal differentiation. In osteoblast, Wnt signaling is impacted, resulting in consequences for both bone formation and resorption. Finally, CFTR could also have a direct role in osteoclasts resorptive function. In this review, we summarize the existing literature on the role of CFTR mutations on the commitment of induced pluripotent stem cells to bone cells.

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