Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis.

ABSTRACT: Recent interest in the control of bone metabolism has focused on a specialized subset of CD31^hiendomucin^hi vessels, which are reported to couple angiogenesis with osteogenesis. However, the underlying mechanisms that link these processes together remain largely undefined. Here we show that the zinc-finger transcription factor ZEB1 is predominantly expressed in CD31^hiendomucin^hi endothelium in human and mouse bone. Endothelial cell-specific deletion of ZEB1 in mice impairs CD31^hiendomucin^hi vessel formation in the bone, resulting in reduced osteogenesis. Mechanistically, ZEB1 deletion reduces histone acetylation on Dll4 and Notch1 promoters, thereby epigenetically suppressing Notch signaling, a critical pathway that controls

SUBMITTER: Fu R 

PROVIDER: S-EPMC6978338 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature