Activation of HIFa pathway in mature osteoblasts disrupts the integrity of the osteocyte/canalicular network
The hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, 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 HIFα signaling. Here we show that inactivation of Vhl in mature osteoblasts/osteocytes induces their apoptosis and disrupts the cell/canalicular network. VHL-deficient (ΔVHL) 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 β-catenin in the BMSC. Our data suggest that the VHL/HIFα 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 β-catenin in the osteoblasts/osteoprogenitors of the bone marrow.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
PloS one - 10(2015), 3 vom: 24., Seite e0121266 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zuo, Gui-lai [VerfasserIn] |
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| Links: |
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| Themen: |
EC 2.3.2.27 |
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| Anmerkungen: |
Date Completed 23.02.2016 Date Revised 13.11.2018 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0121266 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM247404519 |
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| 100 | 1 | |a Zuo, Gui-lai |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Activation of HIFa pathway in mature osteoblasts disrupts the integrity of the osteocyte/canalicular network |
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| 500 | |a Date Revised 13.11.2018 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The hypoxia-inducible factors (HIFs), HIF-1α and HIF-2α, 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 HIFα signaling. Here we show that inactivation of Vhl in mature osteoblasts/osteocytes induces their apoptosis and disrupts the cell/canalicular network. VHL-deficient (ΔVHL) 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 β-catenin in the BMSC. Our data suggest that the VHL/HIFα 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 β-catenin in the osteoblasts/osteoprogenitors of the bone marrow | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Hif1a protein, mouse |2 NLM | |
| 650 | 7 | |a Hypoxia-Inducible Factor 1, alpha Subunit |2 NLM | |
| 650 | 7 | |a Von Hippel-Lindau Tumor Suppressor Protein |2 NLM | |
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| 700 | 1 | |a Zhang, Lian-fang |e verfasserin |4 aut | |
| 700 | 1 | |a Qi, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Jia, Peng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Han-bing |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jin-shen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Nian-dong |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Lian-fu |e verfasserin |4 aut | |
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