@article{283158cddce7434e91f1c150eeece2b0,
title = "Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification",
abstract = "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.",
author = "Charles Hwang and Simone Marini and Huber, {Amanda K.} and Stepien, {David M.} and Michael Sorkin and Shawn Loder and Pagani, {Chase A.} and John Li and Visser, {Noelle D.} and Kaetlin Vasquez and Garada, {Mohamed A.} and Shuli Li and Jiajia Xu and Hsu, {Ching Yun} and Yu, {Paul B.} and James, {Aaron W.} and Yuji Mishina and Shailesh Agarwal and Jun Li and Benjamin Levi",
note = "Funding Information: We would like to thank Christopher Breuler, Caitlin Priest, Serra Ucer, and the University of Michigan Orthopaedic Research Laboratories for their technical assistance. We also thank the Department of Radiology at The University of Michigan for the use of The Center for Molecular Imaging and The Preclinical Imaging & Computational Analysis Shared Resource which are supported in part by Comprehensive Cancer Center NIH grant P30 CA046592. We also thank to the University of Michigan Biomedical Research Core Facilities and the DNA sequencing core. Funding Information: Competing interests: A.W.J. serves on the scientific advisory board for Novadip LLC and also receives laboratory financial support from MTF Biologics for research unrelated to the current project. All other authors declare no competing interests.. Funding Information: B.L.: Supported by funding from NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH1R01AR071379 and American College of Surgeons Clowes Award. D.M.S.: Supported by Plastic Surgery Foundation Resident Research Award. M. S.: Supported by Plastic Surgery Foundation National Endowment Award. C.H.: Supported by Howard Hughes Medical Institute Medical Research Fellowship. J.L.: Supported by Vascular Surgery T32 5-T32-HL-076123–14. A.W.J.: Supported by the NIH/NIAMS (R01 AR070773, K08 AR068316, S10OD016374), the Orthopedic Research and Education Foundation with funding provided by the Maryland Stem Cell Research Foundation, and the Musculoskeletal Transplant Foundation. P.B.Y.: Supported by funding from NIH/NIAMS R01 AR057374 and NHLBI R01 HL131910. Y.M.: Supported by funding from NIH/NIDCR R01 DE020843 and DE027662 Funding Information: Ethics statement All animal experiments described were approved by the University Committee on Use and Care of Animals at the University of Michigan, Ann Arbor (Protocols: #05909 and 07930). This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.59 All animal procedures were carried out in accordance with the guidelines provided in the Guide for the Use and Care of Laboratory Animals: Eighth Edition from the Institute for Laboratory Animal Research.60 Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41413-019-0075-6",
language = "English (US)",
volume = "7",
journal = "Bone Research",
issn = "2095-4700",
publisher = "Nature Publishing Group",
number = "1",
}