EGFR controls bone development by negatively regulating mTOR-signaling during osteoblast differentiation.

ABSTRACT: Mice deficient in epidermal growth factor receptor (Egfr^-/- mice) are growth retarded and exhibit severe bone defects that are poorly understood. Here we show that EGFR-deficient mice are osteopenic and display impaired endochondral and intramembranous ossification resulting in irregular mineralization of their bones. This phenotype is recapitulated in mice lacking EGFR exclusively in osteoblasts, but not in mice lacking EGFR in osteoclasts indicating that osteoblasts are responsible for the bone phenotype. Experiments are presented demonstrating that signaling via EGFR stimulates osteoblast proliferation and inhibits their differentiation by suppression of the IGF-1R/mTOR-pathway via ERK1/2-dependent up-regulation of IGFBP-3. Osteoblasts from Egfr^-/- mice show increa

SUBMITTER: Linder M 

PROVIDER: S-EPMC5988706 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature