Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification

Significance Heterotopic ossification (HO) is a debilitating condition in which bone forms inappropriately within soft tissues. Two vastly different patient populations are at risk for developing HO: those with musculoskeletal trauma or severe burns and those with a genetic mutation in the bone morphogenetic protein receptor ACVR1 (Activin type 1 receptor). In this study, we demonstrate that both forms of HO share a common signaling pathway through hypoxia inducible factor-1α, and that pharmacologic inhibition or genetic knockout of this signaling pathway can mitigate and even abolish HO formation. These findings pave the way for pharmacologic inhibitors of hypoxia inducible factor-1α as therapeutic options for heterotopic ossification.