Hwang Charles, Marini Simone, Huber Amanda K, Stepien David M, Sorkin Michael, Loder Shawn, Pagani Chase A, Li John, Visser Noelle D, Vasquez Kaetlin, Garada Mohamed A, Li Shuli, Xu Jiajia, Hsu Ching-Yun, Yu Paul B, James Aaron W, Mishina Yuji, Agarwal Shailesh, Li Jun, Levi Benjamin
1Department of Surgery, University of Michigan, Ann Arbor, MI 48109 USA.
2Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109 USA.
Bone Res. 2019 Dec 10;7:36. doi: 10.1038/s41413-019-0075-6. eCollection 2019.
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.
异位骨化（HO）是一种以异位骨病理形成为特征的使人衰弱的病症。HO常见于骨科手术、烧伤和神经损伤后。虽然手术切除可能会缓解症状，但由于病理骨的血液供应比正常骨更强，该手术常常伴随着术中大量失血。基于这些临床观察，我们着手研究血管信号传导在HO中的作用。血管内皮生长因子A（VEGFA）先前已被证明在正常骨骼发育和稳态过程中是一种关键的促血管生成和促骨生成信号。我们使用经过验证的HO小鼠模型得出的研究结果表明，HO病变具有高度血管化，并且VEGFA对异位骨形成至关重要，尽管在发育中的原基内缺乏内皮细胞的作用。
