Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification

Charles Hwang, Simone Marini, Amanda K. Huber, David M. Stepien, Michael Sorkin, Shawn Loder, Chase A. Pagani, John Li, Noelle D. Visser, Kaetlin Vasquez, Mohamed A. Garada, Shuli Li, Jiajia Xu, Ching Yun Hsu, Paul B. Yu, Aaron W. James, Yuji Mishina, Shailesh Agarwal, Jun Li, Benjamin Levi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Heterotopic ossification (HO) is a debilitating condition characterized by the pathologic formation of ectopic bone. HO occurs commonly following orthopedic surgeries, burns, and neurologic injuries. While surgical excision may provide palliation, the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone. Based on these clinical observations, we set out to examine the role of vascular signaling in HO. Vascular endothelial growth factor A (VEGFA) has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis. Our findings, using a validated mouse model of HO, demonstrate that HO lesions are highly vascular, and that VEGFA is critical to ectopic bone formation, despite lacking a contribution of endothelial cells within the developing anlagen.

Original languageEnglish
Article number36
JournalBone Research
Issue number1
StatePublished - 1 Dec 2019
Externally publishedYes


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