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

Abstract

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.

Pro-inflammatory activity of long noncoding RNA FOXD2-AS1 in Achilles tendinopathy

“…This study found that after downregulating FOXD2-AS1, the degenerative changes of rat Achilles tendon were alleviated, collagen fiber rupture was reduced, COL1A1 and TNMD expression was increased, and UTS, stiffness, and Young’s modulus of Achilles tendon were increased. Several studies have shown that inflammation is closely related to tendon healing [ 2 , 39 – 42 ], and chronic excessive inflammation promotes tendon degeneration and affects tendon repair and reconstruction [ 43 , 44 ]. TNF-α and IL-6 are typical pro-inflammatory cytokines [ 45 ].…”

Blockage of S100A8/A9 ameliorates septic nephropathy in mice

“…In this research, using Paquinimod ( Talley et al, 2021 ; Zhao et al, 2021 ; Su et al, 2022 ) (Paq, also known as ABR25757), an S100A8/A9 specific inhibitor which prevents S100A8/A9 to bind to TLR4, we explored the role of S100A9 in the development of septic AKI in a murine model of cecal ligation and puncture (CLP)-induced sepsis. We found that S100A9 level was notably regulated upwards in the kidney of CLP-treated mice during 24–72 h. CLP-induced renal dysfunction and pathological alterations, including tubular epithelial cell apoptosis, inflammation, and oxidative stress, was ameliorated by using Paq to inhibition of S100A9 in mice.…”