ArticleRheumatology (Oxford, England)2025
S100A8/A9 drives monocytes towards M2-like macrophage differentiation and associates with M2-like macrophages in osteoarthritic synovium.
Article in Rheumatology (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Macrophage immunometabolic reprogramming in inflammatory repair failure in osteonecrosis of the femoral head.Journal of orthopaedic translation · 2026Review
- Mesenchymal stromal cells immunosuppress osteoarthritis synovial fluid modulated monocytes via IL-6 and CCL2.Cell death & disease · 2026Article
- S100A8/A9 and S100A12 Proteins and Macrophage Polarization: Therapeutic Targets in Atherosclerosis.Biomolecules · 2026Review
- Monocytes strongly induce (myo)fibroblast contraction in a 3D skin model to understand inflammation-fibrosis crosstalk.Scientific reports · 2026Article
- Cellular and molecular landscapes of inflammation in anterior cruciate ligament rupture patients are independent on concurrent meniscal injury.Arthritis research & therapy · 2026Article
- Single-cell and spatial transcriptomics reveal that the CXCL12-CXCR4 axis drives the immune-desert phenotype in small cell lung cancer by recruiting immunosuppressive CXCR4Journal for immunotherapy of cancer · 2026Article
- A Synovium-on-Chip Platform to Study Multicellular Interactions in Arthritis.Advanced healthcare materials · 2026Article
- Thromboxane receptor activation in dendritic cells mitigates sepsis by suppressing S100a8/a9-mediated neutrophil recruitment.Signal transduction and targeted therapy · 2026Article
- Integrated transcriptome and single-cell RNA sequencing identifies small GTPase-associated biomarkers in ulcerative colitis.Frontiers in immunology · 2026Article
- New therapeutic target for osteoarthritis: modulating immune-metabolic aberrations and micromilieu remodeling in underlying bone.Frontiers in pharmacology · 2026Review
- The S100A8/A9-NETosis feedback loop in sepsis: potential mechanisms, immune crosstalk, and therapeutic targeting.Frontiers in immunology · 2026Review
- PADI2 exacerbates Mycoplasma ovipneumoniae-induced lung injury in sheep by suppressing M2 macrophage polarization.Veterinary research · 2025Article
- Observational
- Serum Levels of HMGB1, hS100A8/A9, and sRAGE in Patients with Knee and Hip Osteoarthritis: Inflammatory Biomarkers of Disease Activity.Journal of clinical medicine · 2025Article
- Targeted inhibitors of S100A9 alleviate chronic pancreatitis by inhibiting M2 macrophage polarization via the TAOK3-JNK signaling pathway.Frontiers in immunology · 2025Article
- Soluble immune checkpoint factors reveal high-risk osteosarcoma subtypes and enable early metastasis prediction.Frontiers in immunology · 2025Article
- The Role of Alarmins in the Pathogenesis of Rheumatoid Arthritis, Osteoarthritis, and Psoriasis.Current issues in molecular biology · 2024Review
- Development and Validation of Diagnostic Models for Transcriptomic Signature Genes for Multiple Tissues in Osteoarthritis.Journal of inflammation research · 2024Article
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Authors and funding
15 authors.
Funding
Abstract
objectivesMacrophages are key orchestrators of the osteoarthritis (OA)-associated inflammatory response. Macrophage phenotype is dependent on environmental cues like the inflammatory factor S100A8/A9. Here, we investigated how S100A9 exposure during monocyte-to-macrophage differentiation affects macrophage phenotype and function.
methodsOA synovium cellular composition was determined using flow cytometry and multiplex immunohistochemistry. Healthy donor monocytes were differentiated towards M1- and M2-like macrophages in the presence of S100A9. Macrophage markers were measured using flow cytometry, and phagocytic activity was determined using pHrodo Red Zymosan A BioParticles. Gene expression was determined using qPCR. Protein secretion was measured using Luminex multianalyte analysis and ELISA.
resultsMacrophages were the dominant leucocyte subpopulation in OA synovium. They mainly presented with an M2-like phenotype, although the majority also expressed M1-like macrophage markers. Long-term exposure to S100A9 during monocyte-to-macrophage differentiation increased M2-like macrophage markers CD163 and CD206 in M1-like and M2-like differentiated cells. In addition, M1-like macrophage markers were increased in M1-like, but decreased in M2-like differentiated macrophages. In agreement with this mixed phenotype, S100A9 stimulation modestly increased expression and secretion of pro-inflammatory markers and catabolic enzymes, but also increased expression and secretion of anti-inflammatory/anabolic markers. In accordance with the upregulation of M2-like macrophage markers, S100A9 increased phagocytic activity. Finally, we indeed observed a strong association between S100A8 and S100A9 expression and the M2-like/M1-like macrophage ratio in end-stage OA synovium.
conclusionChronic S100A8/A9 exposure during monocyte-to-macrophage differentiation favours differentiation towards an M2-like macrophage phenotype. The properties of these cells could help explain the catabolic/anabolic dualism in established OA joints with low-grade inflammation.
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