Activation of HIFa pathway in mature osteoblasts disrupts the integrity of the osteocyte/canalicular network.

ABSTRACT: The hypoxia-inducible factors (HIFs), HIF-1? and HIF-2?, are the central mediators of the homeostatic response that enables cells to survive and differentiate in low-oxygen conditions. Previous studies indicated that disruption of the von Hippel-Lindau gene (Vhl) coincides with the activation of HIF? signaling. Here we show that inactivation of Vhl in mature osteoblasts/osteocytes induces their apoptosis and disrupts the cell/canalicular network. VHL-deficient (?VHL) mice exhibited a significantly increased cortical bone area resulting from enhanced proliferation and osteogenic differentiation of the bone marrow stromal cells (BMSCs) by inducing the expression of ?-catenin in the BMSC. Our data suggest that the VHL/HIF? pathway in mature osteoblasts/osteocytes plays a critical role in the bone cell/canalicular network and that the changes of osteocyte morphology/function and cell/canalicular network may unleash the bone formation, The underlying mechanism of which was the accumulation of ?-catenin in the osteoblasts/osteoprogenitors of the bone marrow.

SUBMITTER: Zuo GL 

PROVIDER: S-EPMC4373796 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature