Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte Phenotype
Synovial inflammation is recognised as a pathological driver of osteoarthritis (OA), a degenerative joint disease involving cartilage degradation and joint pain. Since extracellular vesicles (EVs) have emerged as key mediators of cellular cross-talk, this study characterised synovial fluid EVs (SFEV...
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MDPI AG
2025-06-01
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| author | Caitlin Ditchfield Joshua Price Edward T. Davis Simon W. Jones |
| author_facet | Caitlin Ditchfield Joshua Price Edward T. Davis Simon W. Jones |
| author_sort | Caitlin Ditchfield |
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| description | Synovial inflammation is recognised as a pathological driver of osteoarthritis (OA), a degenerative joint disease involving cartilage degradation and joint pain. Since extracellular vesicles (EVs) have emerged as key mediators of cellular cross-talk, this study characterised synovial fluid EVs (SFEVs) in OA patients with varying disease severity and determined their functional effects on OA articular chondrocytes. Synovial fluid and articular cartilage were collected from patients undergoing knee surgery. SFEVs were isolated via ultracentrifugation and characterised by nanoparticle tracking analysis, ExoView, and Luminex analysis of protein cargo. Patients were stratified into mild/moderate- and severe-OA groups based on Oxford Knee Score and EQ5D. Chondrocytes were treated with SFEVs, and transcriptomic and secretome responses were analysed using RNA sequencing, Luminex, and ELISA. SFEVs from patients with severe OA were more abundant, smaller and exhibited increased tetraspanin expression. Synovial fluid and SFEVs induced distinct transcriptomic changes in chondrocytes. SFEVs from patients with severe OA promoted a pro-inflammatory and catabolic chondrocyte phenotype, with upregulation of <i>CRTAC1</i>, <i>COL6A3</i>, <i>TNC</i>, and <i>CXCL5</i>, greater secretion of IL-6, MMP1, MMP3 and MMP13, and pro-nociceptive mediators (NGF and Substance P). These findings suggest that SFEVs may contribute to OA progression by exacerbating cartilage damage and promoting pain sensitisation. |
| format | Article |
| id | doaj-art-d454c9e98f18403ba3f20b0984d22eae |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-d454c9e98f18403ba3f20b0984d22eae2025-08-20T02:24:42ZengMDPI AGBiomolecules2218-273X2025-06-0115682910.3390/biom15060829Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte PhenotypeCaitlin Ditchfield0Joshua Price1Edward T. Davis2Simon W. Jones3Department of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UKDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UKThe Royal Orthopaedic Hospital, Birmingham B31 2AP, UKDepartment of Inflammation and Ageing, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT, UKSynovial inflammation is recognised as a pathological driver of osteoarthritis (OA), a degenerative joint disease involving cartilage degradation and joint pain. Since extracellular vesicles (EVs) have emerged as key mediators of cellular cross-talk, this study characterised synovial fluid EVs (SFEVs) in OA patients with varying disease severity and determined their functional effects on OA articular chondrocytes. Synovial fluid and articular cartilage were collected from patients undergoing knee surgery. SFEVs were isolated via ultracentrifugation and characterised by nanoparticle tracking analysis, ExoView, and Luminex analysis of protein cargo. Patients were stratified into mild/moderate- and severe-OA groups based on Oxford Knee Score and EQ5D. Chondrocytes were treated with SFEVs, and transcriptomic and secretome responses were analysed using RNA sequencing, Luminex, and ELISA. SFEVs from patients with severe OA were more abundant, smaller and exhibited increased tetraspanin expression. Synovial fluid and SFEVs induced distinct transcriptomic changes in chondrocytes. SFEVs from patients with severe OA promoted a pro-inflammatory and catabolic chondrocyte phenotype, with upregulation of <i>CRTAC1</i>, <i>COL6A3</i>, <i>TNC</i>, and <i>CXCL5</i>, greater secretion of IL-6, MMP1, MMP3 and MMP13, and pro-nociceptive mediators (NGF and Substance P). These findings suggest that SFEVs may contribute to OA progression by exacerbating cartilage damage and promoting pain sensitisation.https://www.mdpi.com/2218-273X/15/6/829osteoarthritisextracellular vesiclessynovial fluidarticular chondrocytessynovitis |
| spellingShingle | Caitlin Ditchfield Joshua Price Edward T. Davis Simon W. Jones Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte Phenotype Biomolecules osteoarthritis extracellular vesicles synovial fluid articular chondrocytes synovitis |
| title | Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte Phenotype |
| title_full | Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte Phenotype |
| title_fullStr | Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte Phenotype |
| title_full_unstemmed | Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte Phenotype |
| title_short | Synovial Fluid Extracellular Vesicles from Patients with Severe Osteoarthritis Differentially Promote a Pro-Catabolic, Inflammatory Chondrocyte Phenotype |
| title_sort | synovial fluid extracellular vesicles from patients with severe osteoarthritis differentially promote a pro catabolic inflammatory chondrocyte phenotype |
| topic | osteoarthritis extracellular vesicles synovial fluid articular chondrocytes synovitis |
| url | https://www.mdpi.com/2218-273X/15/6/829 |
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