Endothelial ZEB1 promotes angiogenesis-dependent bone formation and reverses osteoporosis

摘要: Recent interest in the control of bone metabolism has focused on a specialized subset CD31hiendomucinhi vessels, which are reported to couple angiogenesis with osteogenesis. However, underlying mechanisms that link these processes together remain largely undefined. Here we show zinc-finger transcription factor ZEB1 is predominantly expressed endothelium human and mouse bone. Endothelial cell-specific deletion mice impairs vessel formation bone, resulting reduced Mechanistically, reduces histone acetylation Dll4 Notch1 promoters, thereby epigenetically suppressing Notch signaling, critical pathway controls expression skeletal declines osteoporotic humans. Administration Zeb1-packaged liposomes restores impaired activity endothelium, promoting angiogenesis-dependent osteogenesis ameliorating loss. Pharmacological reversal low ZEB1/Notch signaling may exert therapeutic benefit patients by formation.