Inhibition of Hif1α prevents both trauma-induced and genetic heterotopic ossification
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 31, 2015
- Source ID
- 10.1073/pnas.1515397113
Entities
People
- Benjamin Lévi
- Bjorn R. Olsen
- Cameron Brownley
- Christopher Breuler
- David Cholok
- David N. Herndon
- Dolrudee Jumlongras
- Ernestina Schipani
- Hsiao H. Sung
- John Li
- Joshua C Peterson
- Kavitha Ranganathan
- Laura Mangiavini
- Ronald Tompkins
- Shailesh Agarwal
- Shawn Loder
- Shuli Li
- Thomas A. Davis
- Wenzhong Xiao
- Yuji Mishina
Organizations
- Harvard School of Dental Medicine
- Howard Hughes Medical Institute
- Massachusetts General Hospital
- National Institutes of Health
- Naval Medical Research Center
- Plastic Surgery Foundation
- Stanford University
- United States Department of Defense
- University of Michigan
- University of Texas Medical Branch