Inactivation of Vhl in osteochondral progenitor cells causes high bone mass phenotype and protects against age-related bone loss in adult mice.

摘要: Previous studies have shown that disruption of von Hippel–Lindau gene (Vhl) coincides with activation hypoxia-inducible factor α (HIFα) signaling in bone cells and plays an important role development, homeostasis, regeneration. It is known HIF1α mature osteoblasts central to the coupling between angiogenesis formation. However, precise mechanisms responsible for skeletal osteogenesis during remodeling are only partially elucidated. To evaluate Vhl homeostasis vascular physiology bone, we generated mice lacking osteochondral progenitor (referred as cKO mice) at postnatal adult stages a tamoxifen-inducible manner changes morphology were assessed by micro–computed tomography (µCT), histology, histomorphometry. We found inactivation stage largely phenocopied osteoblasts, developing striking progressive accumulation cancellous increased microvascular density These accompanied significant increase osteoblast proliferation, upregulation differentiation marker Runx2 osteocalcin, elevated expression endothelial growth (VEGF) phosphorylation Smad1/5/8. In addition, deletion protects from aging-induced loss. Our data suggest VHL-mediated critical postnatal/adult through angiogenesis. © 2014 American Society Bone Mineral Research.