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

Bone Research
Christophe MerceronErnestina Schipani

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.

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Citations

Jul 10, 2020·Journal of Cellular Physiology·Scott S HannahConor McClean
Sep 15, 2019·Histochemistry and Cell Biology·Jan BobekEva Matalova
Mar 23, 2021·Journal of Cellular Physiology·Xiangguo CheJe-Yong Choi

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Methods Mentioned

BETA
genotyping
ELISA

Software Mentioned

Bioquant Osteo
JASPAR
Ensembl !
Microview

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