Hypoxia-inducible factor 2α is a negative regulator of osteoblastogenesis and bone mass accrual

Christophe Merceron, Kavitha Ranganathan, Elizabeth Wang, Zachary Tata, Shreya Makkapati, Mohd Parvez Khan, Laura Mangiavini, Angela Qing Yao, Laura Castellini, Benjamin Levi, Amato J. Giaccia, Ernestina Schipani

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number7
JournalBone Research
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

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