Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification  

作　　者：Charles Hwang Simone Marini Amanda KHuber David MStepien Michael Sorkin Shawn Loder Chase APagani John Li Noelle DVisser Kaetlin Vasquez Mohamed AGarada Shuli Li Jiajia Xu Ching-Yun Hsu Paul BYu Aaron WJames Yuji Mishina Shailesh Agarwal Jun Li Benjamin Levi 

机构地区：[1]Department of Surgery,University of Michigan,Ann Arbor,MI 48109,USA [2]Department of Computational Medicine and Bioinformatics,University of Michigan,Ann Arbor,MI 48109,USA [3]Department of Pathology,Johns Hopkins University,Baltimore,MD 21218,USA [4]Division of Cardiovascular Medicine,Department of Medicine,Brigham and Women’s Hospital,Harvard Medical School,Boston,MA 02115,USA [5]Department of Biologic and Materials Sciences&Prosthodontics,School of Dentistry,University of Michigan,Ann Arbor,MI 48109,USA

出　　处：《Bone Research》2019年第4期371-387,共17页骨研究（英文版）

基　　金：B.L.:Supported by funding from NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH1R01AR071379;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

摘　　要：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.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.

关 键 词：VEGFA INJURIES OSSIFICATION 

分 类 号：R68[医药卫生—骨科学]