PMID- 34988207 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220429 IS - 2305-5839 (Print) IS - 2305-5847 (Electronic) IS - 2305-5839 (Linking) VI - 9 IP - 22 DP - 2021 Nov TI - Role of the Alarmin S100A9 protein in inducing Achilles tendinopathy in rats. PG - 1698 LID - 10.21037/atm-21-5945 [doi] LID - 1698 AB - 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. CI - 2021 Annals of Translational Medicine. All rights reserved. FAU - Zhao, Bin-An AU - Zhao BA AD - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Li, Jun AU - Li J AD - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Xue, Chao AU - Xue C AD - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Li, Jie AU - Li J AD - Department of Orthopedics, Shanghai Zhabei District Central Hospital, Shanghai, China. FAU - Ge, Heng-An AU - Ge HA AD - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Cheng, Biao AU - Cheng B AD - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. FAU - Su, Qi-Hang AU - Su QH AD - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. LA - eng PT - Journal Article PL - China TA - Ann Transl Med JT - Annals of translational medicine JID - 101617978 PMC - PMC8667095 OTO - NOTNLM OT - Achilles tendinopathy (AT) OT - Alarmin S100A9 OT - animal experiment OT - degeneration OT - inflammation COIS- 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. EDAT- 2022/01/07 06:00 MHDA- 2022/01/07 06:01 PMCR- 2021/11/01 CRDT- 2022/01/06 06:00 PHST- 2021/10/09 00:00 [received] PHST- 2021/11/19 00:00 [accepted] PHST- 2022/01/06 06:00 [entrez] PHST- 2022/01/07 06:00 [pubmed] PHST- 2022/01/07 06:01 [medline] PHST- 2021/11/01 00:00 [pmc-release] AID - atm-09-22-1698 [pii] AID - 10.21037/atm-21-5945 [doi] PST - ppublish SO - Ann Transl Med. 2021 Nov;9(22):1698. doi: 10.21037/atm-21-5945.