ArticleBMJ open sport & exercise medicine2017
Differential expression of alarmins-S100A9, IL-33, HMGB1 and HIF-1α in supraspinatus tendinopathy before and after treatment.
Article in BMJ open sport & exercise medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- Proteomic trajectories in human rotator cuff degeneration: a systematic review of immunohistochemical studies.Journal of orthopaedic surgery and research · 2026Pooled it
- A systematic review of inflammatory cells and markers in human tendinopathy.BMC musculoskeletal disorders · 2020Pooled it
- Trial
- Effects of Mechanical Loading on the Structure and Function of the Achilles Tendon: From Homeostatic Adaptation to Pathological Degeneration.Journal of functional morphology and kinesiology · 2026Review
- The HMGB1/RAGE/β-catenin axis mediates aberrant osteogenic-tenogenic differentiation imbalance of tendon stem/progenitor cells in diabetic tendinopathy.Journal of orthopaedic surgery and research · 2025Article
- Metformin lotion as a novel approach to prevent tendinopathy induced by mechanical overuse.Scientific reports · 2025Article
- Achilles tendinopathy.Nature reviews. Disease primers · 2025Review
- Assessing Bioprinted Functionalized Grafts for Biological Tendon Augmentation In Vitro.International journal of molecular sciences · 2024Article
- Hypoxia-Inducible Factor and Oxidative Stress in Tendon Degeneration: A Molecular Perspective.Antioxidants (Basel, Switzerland) · 2024Review
- HMGB1 Modulates High Glucose-Induced Erroneous Differentiation of Tendon Stem/Progenitor Cells through RAGE/Stem cells international · 2024Article
- miRNAs contributing to the repair of tendon injury.Cell and tissue research · 2023Review
- Metformin improves tendon degeneration by blocking translocation of HMGB1 and suppressing tendon inflammation and senescence in aging mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- S100A9 plays a key role in Clostridium perfringens beta2 toxin-induced inflammatory damage in porcine IPEC-J2 intestinal epithelial cells.BMC genomics · 2023Article
- Karyopherins in the Remodeling of Extracellular Matrix: Implications in Tendon Injury.Journal of orthopaedics and sports medicine · 2023Article
- Review
- The role of loading in murine models of rotator cuff disease.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022Article
- Pathological Tendon Histology in Early and Chronic Human Patellar Tendinopathy.Translational sports medicine · 2022Article
- Inflammatory mechanisms linking obesity and tendinopathy.Journal of orthopaedic translation · 2021Review
- Bringing tendon biology to heel: Leveraging mechanisms of tendon development, healing, and regeneration to advance therapeutic strategies.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Review
- Multi-omic single cell analysis resolves novel stromal cell populations in healthy and diseased human tendon.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlarmins, endogenous molecules released on tissue damage have been shown to play an important role in inflammatory musculoskeletal conditions including fracture repair andrheumatoid arthritis. However, the contribution of alarmins to the pathogenesis of tendon disease is not fully understood.
methodsWe investigated expression of alarmin proteins (S100A9, high-mobility group box 1 (HMGB1) and interleukin-33 (IL-33) and hypoxia-inducible factor 1α (HIF-1α), a subunit of an oxygen sensitive transcription factor, in three cohorts of human supraspinatus tissues: healthy (n=6), painful diseased (n=13) and post-treatment pain-free tendon samples (n=5). Tissue samples were collected during shoulder stabilisation surgery (healthy) or by biopsy needle (diseased/treated). Immunohistochemistry was used to investigate the protein expression of these factors in these healthy, diseased and treated tendons. Kruskal-Wallis with pairwise post hoc Mann-Whitney U tests were used to test for differences in immunopositive staining between these tissue cohorts. Additionally, costaining was performed to identify the cell types expressing HIF-1α, S100A9, IL-33 and HMGB1 in diseased tendons.
resultsImmunostaining showed HIF-1α and S100A9 were increased in diseased compared with healthy and post-treatment pain-free tendons (p<0.05). IL-33 was reduced in diseased compared with healthy tendons (p=0.0006). HMGB1 was increased in post-treatment pain-free compared with healthy and diseased tendons (p<0.01). Costaining of diseased tendon samples revealed that HIF-1α, S100A9 and IL-33 were expressed by CD68+ and CD68- cells, whereas HMGB1 was predominantly expressed by CD68- cells.
conclusionsThis study provides insight into the pathways contributing to the progressionand resolution of tendon disease. We found potential pro-inflammatory and pathogenic roles for HIF-1α and S100A9, a protective role fornuclear IL-33 and a potentially reparative function for HMGB1 in diseased supraspinatus tendons.
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