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.