Expression of alarmins in a murine rotator cuff tendinopathy model
Expression of alarmins in a murine rotator cuff tendinopathy model
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DOI：
10.1002/jor.24690
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发表时间：
2020-04
期刊：
影响因子：
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通讯作者：
Ying Zhang;Xiang-Hua Deng;Amir Lebaschi;Susumu Wada;C. Carballo;Brett Croen;L. Ying;S. Rodeo
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文献类型：
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作者：
Ying Zhang;Xiang-Hua Deng;Amir Lebaschi;Susumu Wada;C. Carballo;Brett Croen;L. Ying;S. Rodeo
这项研究的目的是研究在一种新的小鼠肩袖肌腱病模型中警报的存在。警报已经被描述为对组织损伤的免疫反应的必要的早期激活剂。在37只雄性C57BL/6小鼠的肩峰下间隙放置一个小的金属夹，在双肩处诱发肩峰下撞击。动物被分配到不同的时间点，长达6周。用苏木精-伊红染色、阿尔新蓝和天狼星红评价冈上肌腱的形态和细胞密度。采用免疫组织化学染色和定量聚合酶链式反应方法检测脑组织中白细胞介素33(IL-33)、c(HMGB1)、缺氧诱导因子-1亚单位α(α)和S100A9的表达和定位。撞击组HMGB1和IL-33阳性细胞百分率在1w、4w和6w时显著增加。撞击组1w和6w时HIF1α染色强度均高于对照组。HMGB1基因表达在撞击5d组和撞击6w组较高。撞击组各时间点(5d、2w、4w、6w)HIF1α基因表达均上调。5d撞击组S100A9基因表达上调。这是第一次使用可复制的动物模型证明警报蛋白参与肌腱病早期阶段的研究。Alarmins可能在肌腱病的早期发展中起重要作用，它们可能是肌腱病治疗的潜在靶点。
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.