Cystic Fibrosis Bone Disease: The Interplay between CFTR Dysfunction and Chronic Inflammation

Abstract

Cystic fibrosis is a monogenic disease with a multisystemic phenotype, ranging from predisposition to chronic lung infection and inflammation to reduced bone mass. The exact mechanisms unbalancing the maintenance of an optimal bone mass in cystic fibrosis patients remain unknown. Multiple factors may contribute to severe bone mass reduction that, in turn, have devastating consequences in the patients’ quality of life and longevity. Here, we will review the existing evidence linking the CFTR dysfunction and cell-intrinsic bone defects. Additionally, we will also address how the proinflammatory environment due to CFTR dysfunction in immune cells and chronic infection impairs the maintenance of an adequate bone mass in CF patients.

Chronic Lung Inflammation Leads to Myeloid Skewing of Hematopoietic Stem Cells in a Cystic Fibrosis Mouse Model

“…12 CF pathology is also characterized by bone disease, marked by a reduction in bone density with reduced osteoclasts and osteoblasts activity. 13 The CF bone phenotype can also be observed in the Cftr-/mouse model. 14 Thus, an altered HSC niche, such as the CF bone disease, may impact HSPC independently of infections or inflammatory triggers.…”