| First Author | Zuo GL | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 3 | Pages | e0121266 |
| PubMed ID | 25806791 | Mgi Jnum | J:229265 |
| Mgi Id | MGI:5751357 | Doi | 10.1371/journal.pone.0121266 |
| Citation | Zuo GL, et al. (2015) Activation of HIFa pathway in mature osteoblasts disrupts the integrity of the osteocyte/canalicular network. PLoS One 10(3):e0121266 |
| abstractText | The hypoxia-inducible factors (HIFs), HIF-1alpha and HIF-2alpha, 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 HIFalpha signaling. Here we show that inactivation of Vhl in mature osteoblasts/osteocytes induces their apoptosis and disrupts the cell/canalicular network. VHL-deficient (DeltaVHL) 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 beta-catenin in the BMSC. Our data suggest that the VHL/HIFalpha 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 beta-catenin in the osteoblasts/osteoprogenitors of the bone marrow. |
