Expression of Alarmins in a Murine Rotator Cuff Tendinopathy Model.

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. Sub-acromial 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 was evaluated by hematoxylin-eosin (H&E) staining, alcian blue and picrosirius red. The expression and localization of alarmins interleukin-33 (IL-33), high-mobility group box1 (HMGB1), hypoxia inducible factor-1 subunit alpha (HIF1α), and S100A9 were evaluated by immunohistochemical staining and qPCR. 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). Expression of 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 Alarmins may represent potential therapeutic targets for treatment of tendinopathy. This article is protected by copyright. All rights reserved.