{
  "abstract": "Background: Osteoarthritis (OA) is a whole-joint pathological condition driven by an intricate signaling network among immune cells, articular chondrocytes (ACs), fibroblast-like synoviocytes (FLSs) and non-immune synovial fluid cells (SFCs). While AC and FLS secretomes are well-characterized, the phenotypic identity of SFCs and their signaling cross-talk with structural joint cells remain poorly defined. This study aimed to comparatively characterize the secretome and extracellular vesicles (EVs) profile of donor-matched human ACs, FLSs and SFCs to identify shared and cell-specific signaling features within the osteoarthritic joint. Methods: Primary donor-matched ACs, FLSs and SFCs were isolated from five human osteoarthritic joints. EVs and soluble secretomes were isolated and analyzed by EV surface marker immunophenotyping, EV-microRNAs (miRNAs) profiling and soluble factor analysis. Data were evaluated using principal component analysis, hierarchical clustering, correlation matrices and bioinformatic analyses. Results: All three cell types shared a baseline OA secretome fingerprint dominated by inflammatory and catabolic factors. However, AC secretomes segregated distinctly. FLSs and SFCs displayed high phenotypic correlation across EV surface markers (r = 0.95), EV-miRNA signatures (r = 0.94) and soluble factor profiles (r = 0.94). Bioinformatic analyses showed that upregulated EV-miRNAs shared between FLSs and SFCs were specifically involved with pathways related to immune cell activation, cytokine signaling and apoptosis. In contrast, ACs demonstrated a distinct profile marked by the significant upregulation of soluble catabolic and pro-inflammatory mediators. Conclusions: Non-immune SFCs closely resemble FLSs in their secretome and EV profiles, supporting a similar phenotype and a potential role in EV-mediated immune and inflammatory signaling. In contrast, ACs display a distinct profile characterized by soluble catabolic and pro-inflammatory mediators. These findings highlight compartment-specific signaling patterns within the osteoarthritic joint and may inform future cell-free therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratorio di Biotecnologie Applicate all’Ortopedia, IRCCS Ospedale Galeazzi—Sant’Ambrogio, Via Cristina Belgioioso 173, 20157 Milano, Italy",
    "Laboratory of Biotechnological Applications, IRCCS Ospedale Galeazzi—Sant’Ambrogio, Via Cristina Belgioioso 173, 20157 Milano, Italy",
    "Department of Chirurgia Articolare Sostitutiva e Chirurgia Ortopedica, IRCCS Ospedale Galeazzi—Sant’Ambrogio, Via Cristina Belgioioso 173, 20157 Milano, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Enrico Ragni",
      "orcid": "0000-0003-0272-7417"
    },
    {
      "affs": [
        0
      ],
      "name": "Paola De Luca",
      "orcid": "0000-0001-9810-8818"
    },
    {
      "affs": [
        0
      ],
      "name": "Michela Maria Taiana",
      "orcid": "0000-0001-8257-8831"
    },
    {
      "affs": [
        1
      ],
      "name": "Elena Della Morte",
      "orcid": "0000-0003-1361-168X"
    },
    {
      "affs": [
        2
      ],
      "name": "Federico Valli"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura de Girolamo",
      "orcid": "0000-0002-9979-3092"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0fydyw1msg6fy.bib",
  "cited_by": 0,
  "doi": "10.3390/jcm15218403",
  "fulltext_url": null,
  "id": "0fydyw1msg6fy",
  "issns": [
    "2077-0383"
  ],
  "landing_url": "https://www.mdpi.com/2077-0383/15/21/8403",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
  ],
  "openalex": "W7224099025",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/0fydyw1msg6fy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:01Z",
      "native_id": "10.3390/jcm15218403",
      "source": "crossref",
      "url": "https://www.mdpi.com/2077-0383/15/21/8403"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "The Soluble Secretome and Extracellular Vesicles of Synovial Fluid Cells Closely Resemble Synovial Membrane Fibroblasts over Articular Chondrocytes in Donor-Matched Isolates from Osteoarthritis Patients",
  "title_text": "The Soluble Secretome and Extracellular Vesicles of Synovial Fluid Cells Closely Resemble Synovial Membrane Fibroblasts over Articular Chondrocytes in Donor-Matched Isolates from Osteoarthritis Patients",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:01Z",
  "url": "https://research.draconitic.com/paper/0fydyw1msg6fy",
  "venue": "Journal of Clinical Medicine",
  "versions": []
}