Role of the Alarmin S100A9 protein in inducing Achilles tendinopathy in rats.

Background: This study aimed to investigate the correlation between the Alarmin S100A9 protein and Achilles tendinopathy (AT), and to reveal the role of this protein in inducing AT.
Methods: In this study, 40 male Sprague-Dawley rats were randomly divided into four groups: Control group (received no treatment), Injury group (Achilles tendon tissues were cut intraoperatively), S100A9 group (received a subcutaneous injection of rhS100A9 solution), and S100A9 + Paquinimod group [received a subcutaneous injection of rhS100A9 and Paquinimod (1:1 ratio) into the Achilles tendon]. At 1 week postoperatively, the four groups of rats were euthanized, and the Achilles tendon tissues were isolated for histological staining, immunohistochemistry (IHC), immunofluorescence, Sirius Red (SR) staining, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay.
Results: Compared with both the Control and S100A9 + Paquinimod groups, the Injury and S100A9 groups exhibited higher expression levels of S100A9 protein, matrix metalloproteinase-3 (MMP-3), and inflammatory factors. Regarding histomorphology [hematoxylin-eosin (HE) staining and Safranin O/fast green (SOFG; fast green and Safranin) training], the Achilles tendon tissues in the Injury and S100A9 groups showed AT-like changes, and the fibers were extremely disorderly, non-bundled, and ruptured, and some nuclei were spindles. As for collagen (Col) remodeling, a large number of fresh collagen fibers had formed, the amounts of Col-I and Col-II were lower, and a large quantity of Col-III was present. Additionally, a large number of tendon cells had died in both the Injury and S100A9 groups.
Conclusions: This study showed that Alarmin S100A9 can induce AT-like morphological changes and local inflammatory reactions, trigger collagen fiber remodeling and tendon cell apoptosis, and ultimately induce AT.
Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-5945). The authors have no conflicts of interest to declare.
(2021 Annals of Translational Medicine. All rights reserved.)