Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, New York.
School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
J Orthop Res. 2020 Nov;38(11):2513-2520. doi: 10.1002/jor.24690. Epub 2020 Apr 26.
The aim of this study was to investigate the presence of alarmins in a novel murine rotator cuff tendinopathy model. Alarmins have been described as essential early activators of an immune response to tissue damage. Subacromial impingement was induced in both shoulders of 37 male C57Bl/6 mice by placement of a small metal clip in the subacromial space. Animals were allocated to different time points up to 6 weeks. The morphology and cellularity of the supraspinatus tendon were evaluated by hematoxylin-eosin staining, alcian blue, and picrosirius red. The expression and localization of alarmins interleukin-33 (IL-33), c (HMGB1), hypoxia-inducible factor-1 subunit α (HIF1α), and S100A9 were evaluated by immunohistochemical staining and quantitative polymerase chain reaction. The percentage of positively stained cells with HMGB1 and IL-33 was significantly increased in the impingement group at 1w, 4w, and 6w. HIF1α staining was higher in the impingement group at 1w and 6w compared with the control group. HMGB1 gene expression was higher in the 5d impingement group and 6w impingement group. The gene expression of HIF1α was upregulated at all-time points in the impingement group (5d, 2w, 4w, and 6w). The expression of the S100A9 gene was also upregulated in the 5d impingement group. This is the first study to demonstrate the involvement of alarmins in the early phase of tendinopathy using a reproducible animal model. Alarmins may play an important role in the early phases of the development of tendinopathy They may represent potential therapeutic targets for treatment of tendinopathy.
本研究旨在探讨新型鼠肩袖肌腱病模型中警报素的存在。警报素被描述为组织损伤后免疫反应的早期必需激活物。通过在肩峰下间隙放置小金属夹,在 37 只雄性 C57Bl/6 小鼠的双侧肩峰下引起撞击。动物被分配到不同的时间点,最长可达 6 周。通过苏木精-伊红染色、阿利新蓝和苦味酸天狼星红染色评估冈上肌腱的形态和细胞成分。通过免疫组织化学染色和定量聚合酶链反应评估警报素白细胞介素-33(IL-33)、c(HMGB1)、缺氧诱导因子-1 亚单位α(HIF1α)和 S100A9 的表达和定位。HMGB1 和 IL-33 的阳性染色细胞百分比在撞击组的 1w、4w 和 6w 时显著增加。与对照组相比,撞击组在 1w 和 6w 时 HIF1α 染色更高。HMGB1 基因表达在撞击组的 5d 撞击组和 6w 撞击组中较高。在撞击组的所有时间点(5d、2w、4w 和 6w),HIF1α 基因表达均上调。S100A9 基因的表达在 5d 撞击组中也上调。这是第一项使用可重复动物模型证明警报素参与肌腱病早期阶段的研究。警报素可能在肌腱病的早期阶段发挥重要作用,它们可能是治疗肌腱病的潜在治疗靶点。