Hypoxia-inducible Factor 2α is a Negative Regulator of Osteoblastogenesis and Bone Mass Accrual

Overview

Journal Bone Res

Specialties Endocrinology
Orthopedics

Date 2019 Feb 23

PMID 30792937

Citations 30

Authors

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

Affiliations

Soon will be listed here.

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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