Lüthje Freja Lea, Skovgaard Kerstin, Jensen Henrik Elvang, Kruse Jensen Louise
1 Department of Veterinary and Animal Science, University of Copenhagen, Denmark.
2 Department of Biotechnology and Biomedicine, Technical University of Denmark, Denmark.
Lab Anim. 2018 Dec;52(6):630-640. doi: 10.1177/0023677218766391. Epub 2018 Apr 13.
Pigs are used with increased frequency to model different kinds of orthopedic surgical conditions. In order to show the full potential of porcine models in orthopedic research, it is therefore required to examine the expression of bone regulatory genes in pigs affected by orthopedic surgery and compare it to the expression in humans and mice as mice, are one of the most applied animal species in orthopedics today. In the present study, the local molecular response to drilling of a tibial implant cavity, and the subsequent insertion of a steel implant was examined in a porcine model. Pigs were euthanized five days after drilling of the bone. The molecular response of 73 different genes was analyzed using a high-throughput quantitative polymerase chain reaction platform and compared to histopathology. Histologically, it was found that bone remodeling was initiated on day 5 after surgery and was associated with upregulation of several genes involved in bone degradation and formation ( CTSK, ACP5, IBSP, RANK, RANKL and COL1A1). Interleukin-6 and several acute-phase proteins (C3, SAA and ITIH4) were significantly upregulated, indicating their importance in the initial process of healing and osseointegration. All tested bone morphogenic proteins (BMP2, -4 and -7) including their inhibitor noggin were also significantly upregulated. Surprisingly, vascular endothelial growth factor A was not found to be regulated five days after surgery while several other vascular growth factors (ANGPT1, ANGPT2 and PTN) were upregulated. The pig was found to be a useful model for elucidation of bone regulatory genes in humans.
猪越来越频繁地被用于模拟各种骨科手术情况。为了展现猪模型在骨科研究中的全部潜力,因此需要检测受骨科手术影响的猪体内骨调节基因的表达,并将其与人类和小鼠的表达进行比较,因为小鼠是当今骨科中应用最广泛的动物物种之一。在本研究中,在猪模型中检测了胫骨植入腔钻孔及随后插入钢植入物后的局部分子反应。在骨钻孔五天后对猪实施安乐死。使用高通量定量聚合酶链反应平台分析了73种不同基因的分子反应,并与组织病理学进行比较。组织学上发现,术后第5天开始骨重塑,且与参与骨降解和形成的几种基因(CTSK、ACP5、IBSP、RANK、RANKL和COL1A1)的上调有关。白细胞介素-6和几种急性期蛋白(C3、SAA和ITIH4)显著上调,表明它们在愈合和骨整合初始过程中的重要性。所有测试的骨形态发生蛋白(BMP2、-4和-7)包括其抑制剂头蛋白也显著上调。令人惊讶的是,术后五天未发现血管内皮生长因子A受到调节,而其他几种血管生长因子(ANGPT1、ANGPT2和PTN)上调。发现猪是阐明人类骨调节基因的有用模型。