Cargando…
Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual
Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. HIF1 is known to be a positive regulator of bone formation....
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382776/ https://www.ncbi.nlm.nih.gov/pubmed/30792937 http://dx.doi.org/10.1038/s41413-019-0045-z |
_version_ | 1783396714878599168 |
---|---|
author | Merceron, Christophe Ranganathan, Kavitha Wang, Elizabeth Tata, Zachary Makkapati, Shreya Khan, Mohd Parvez Mangiavini, Laura Yao, Angela Qing Castellini, Laura Levi, Benjamin Giaccia, Amato J. Schipani, Ernestina |
author_facet | Merceron, Christophe Ranganathan, Kavitha Wang, Elizabeth Tata, Zachary Makkapati, Shreya Khan, Mohd Parvez Mangiavini, Laura Yao, Angela Qing Castellini, Laura Levi, Benjamin Giaccia, Amato J. Schipani, Ernestina |
author_sort | Merceron, Christophe |
collection | PubMed |
description | Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. HIF1 is known to be a positive regulator of bone formation. Conversely, the role of HIF2 in the control osteoblast biology is still poorly understood. In this study, we used mouse genetics to demonstrate that HIF2 is an inhibitor of osteoblastogenesis and bone mass accrual. Moreover, we provided evidence that HIF2 impairs osteoblast differentiation at least in part, by upregulating the transcription factor Sox9. Our findings constitute a paradigm shift, as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone formation through HIF1. Inhibiting HIF2 could thus represent a therapeutic approach for the treatment of the low bone mass observed in chronic diseases, osteoporosis, or aging. |
format | Online Article Text |
id | pubmed-6382776 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63827762019-02-21 Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual Merceron, Christophe Ranganathan, Kavitha Wang, Elizabeth Tata, Zachary Makkapati, Shreya Khan, Mohd Parvez Mangiavini, Laura Yao, Angela Qing Castellini, Laura Levi, Benjamin Giaccia, Amato J. Schipani, Ernestina Bone Res Article Osteoblasts, which are the bone-forming cells, operate in a hypoxic environment. The transcription factors hypoxia-inducible factor-1α (HIF1) and HIF2 are key mediators of the cellular response to hypoxia. Both are expressed in osteoblasts. HIF1 is known to be a positive regulator of bone formation. Conversely, the role of HIF2 in the control osteoblast biology is still poorly understood. In this study, we used mouse genetics to demonstrate that HIF2 is an inhibitor of osteoblastogenesis and bone mass accrual. Moreover, we provided evidence that HIF2 impairs osteoblast differentiation at least in part, by upregulating the transcription factor Sox9. Our findings constitute a paradigm shift, as activation of the hypoxia-signaling pathway has traditionally been associated with increased bone formation through HIF1. Inhibiting HIF2 could thus represent a therapeutic approach for the treatment of the low bone mass observed in chronic diseases, osteoporosis, or aging. Nature Publishing Group UK 2019-02-21 /pmc/articles/PMC6382776/ /pubmed/30792937 http://dx.doi.org/10.1038/s41413-019-0045-z Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Merceron, Christophe Ranganathan, Kavitha Wang, Elizabeth Tata, Zachary Makkapati, Shreya Khan, Mohd Parvez Mangiavini, Laura Yao, Angela Qing Castellini, Laura Levi, Benjamin Giaccia, Amato J. Schipani, Ernestina Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual |
title | Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual |
title_full | Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual |
title_fullStr | Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual |
title_full_unstemmed | Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual |
title_short | Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual |
title_sort | hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382776/ https://www.ncbi.nlm.nih.gov/pubmed/30792937 http://dx.doi.org/10.1038/s41413-019-0045-z |
work_keys_str_mv | AT merceronchristophe hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT ranganathankavitha hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT wangelizabeth hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT tatazachary hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT makkapatishreya hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT khanmohdparvez hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT mangiavinilaura hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT yaoangelaqing hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT castellinilaura hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT levibenjamin hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT giacciaamatoj hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual AT schipaniernestina hypoxiainduciblefactor2aisanegativeregulatorofosteoblastogenesisandbonemassaccrual |