体内人创伤后异位骨化模型显示早期纤维增殖特征。
In vivo model of human post-traumatic heterotopic ossification demonstrates early fibroproliferative signature.
机构信息
Department of Surgery, Walter Reed National Military Medical Center & Uniformed Services University of Health Sciences, 4801 Rockville Pike, Bethesda, MD, 20889, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD, 20817, USA.
出版信息
J Transl Med. 2019 Aug 2;17(1):248. doi: 10.1186/s12967-019-1996-y.
BACKGROUND
The relationship between the tissue injury healing response and development of heterotopic ossification (HO) is poorly understood. Here we compare a rat blast model and human traumatized muscle from a blast injury to study the early signatures of osteogenesis and fibrosis during the formation of HO.
METHODS
Rat and human tissues were characterized using histology, scanning electron microscopy, immunohistochemistry, as well as gene and protein expression analysis. Additionally, animals and humans were assessed radiographically for HO formation following injury.
RESULTS
Markers of bone formation were dramatically increased in tissue samples from both humans and rats, and both displayed increased fibroproliferative regions within the injured tissues and elevated expression of markers of tissue fibrosis such as TGF-β1, Fibronectin, SMAD3 and PAI-1. Markers of inflammation and fibrosis (ACTA, TNFα, BMP1 and BMP3) were elevated at the RNA level in both rat and human samples. By day 42, bone formation in the rat blast model appeared similar in radiographs compared to human patients who progressed to develop post-traumatic HO.
CONCLUSIONS
Our data demonstrates that a similar early fibrotic response is evident in both the rat blast model and the human tissues following a traumatic injury and demonstrates the relevance of this animal model for future translational studies.
背景
组织损伤愈合反应与异位骨化（HO）的发展之间的关系尚未完全阐明。在这里，我们比较了大鼠爆炸模型和人因爆炸伤的肌肉组织，以研究 HO 形成过程中成骨和纤维化的早期特征。
方法
使用组织学、扫描电子显微镜、免疫组织化学以及基因和蛋白表达分析对大鼠和人组织进行了特征描述。此外，还对动物和人进行了放射学评估，以确定损伤后 HO 的形成情况。
结果
大鼠和人类组织样本中的骨形成标志物显著增加，且两者在损伤组织中均显示出增加的纤维增生区域，并升高了 TGF-β1、纤连蛋白、SMAD3 和 PAI-1 等组织纤维化标志物的表达。大鼠和人样本中的炎症和纤维化标志物（ACTA、TNFα、BMP1 和 BMP3）在 RNA 水平上均升高。在第 42 天，大鼠爆炸模型中的骨形成在放射照片上与进展为创伤后 HO 的人类患者相似。
结论
我们的数据表明，在创伤后，大鼠爆炸模型和人组织中均出现类似的早期纤维化反应，证明了该动物模型在未来转化研究中的相关性。
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