Orthopedics, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linkoping University, Linköping, Sweden
Orthopedics, Department of Clinical and Experimental Medicine, Faculty of Health Science, Linkoping University, Linköping, Sweden.
J Appl Physiol (1985). 2017 Oct 1;123(4):800-815. doi: 10.1152/japplphysiol.00323.2017. Epub 2017 Jul 13.
Mechanical loading stimulates tendon healing both when applied in the inflammatory phase and in the early remodeling phase of the process, although not necessarily via the same mechanisms. We investigated the gene response to mechanical loading in these two phases of tendon healing. The right Achilles tendon in rats was transected, and the hindlimbs were unloaded by tail suspension. The rats were exposed to 5 min of treadmill running 3 or 14 days after tendon transection. Thereafter, they were resuspended for 15 min or 3 h until euthanasia. The controls were suspended continuously. Gene analysis was first performed by microarray analysis followed by quantitative RT-PCR on selected genes, focusing on inflammation. Fifteen minutes after loading, the most important genes seemed to be the transcription factors EGR1 and C-FOS, regardless of healing phase. These transcription factors might promote tendon cell proliferation and differentiation, stimulate collagen production, and regulate inflammation. Three hours after loading on , inflammation was strongly affected. Seven inflammation-related genes were upregulated according to PCR: CCL20, CCL7, IL-6, NFIL3, PTX3, SOCS1, and TLR2. These genes can be connected to macrophages, T cells, and recruitment of leukocytes. According to Ingenuity Pathway Analysis, the recruitment of leukocytes was increased by loading on , which also was confirmed by histology. This inflammation-related gene response was not seen on Our results suggest that the immediate gene response after mechanical loading is similar in the early and late phases of healing but the late gene response is different. This study investigates the direct effect of mechanical loading on gene expression during different healing phases in tendon healing. One isolated episode of mechanical loading was studied in otherwise unloaded healing tendons. This enabled us to study a time sequence, i.e., which genes were the first ones to be regulated after the loading episode.
力学加载在肌腱愈合的炎症期和早期重塑期均能刺激肌腱愈合，尽管其作用机制可能不同。我们研究了力学加载在肌腱愈合的这两个阶段对基因的反应。在大鼠的右侧跟腱切断后，通过尾巴悬吊使后肢去负荷。在肌腱切断后 3 或 14 天，大鼠接受 5 分钟的跑步机跑步。之后，它们被重新悬吊 15 分钟或 3 小时，直到安乐死。对照组则持续悬吊。首先通过微阵列分析进行基因分析，然后对选定的基因（重点是炎症）进行定量 RT-PCR。在加载后 15 分钟，最重要的基因似乎是转录因子 EGR1 和 C-FOS，而与愈合阶段无关。这些转录因子可能促进肌腱细胞增殖和分化，刺激胶原产生，并调节炎症。在加载后 3 小时，炎症受到强烈影响。根据 PCR，有 7 个炎症相关基因上调：CCL20、CCL7、IL-6、NFIL3、PTX3、SOCS1 和 TLR2。这些基因可以与巨噬细胞、T 细胞和白细胞募集相关联。根据 Ingenuity 通路分析，加载后白细胞的募集增加，组织学也证实了这一点。在加载后 15 分钟时未观察到这种炎症相关基因反应。我们的结果表明，机械加载后的即刻基因反应在愈合的早期和晚期阶段相似，但晚期基因反应不同。本研究探讨了在肌腱愈合的不同愈合阶段，机械加载对基因表达的直接影响。在未加载的愈合肌腱中，研究了一个孤立的力学加载事件。这使我们能够研究一个时间序列，即在加载事件后哪些基因首先被调控。
