{
  "abstract": "Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, cartilage degradation, and bone erosion. Fibroblast-like synoviocytes (FLS) play a central role in perpetuating joint damage, yet current therapies inadequately address FLS-driven pathology. Existing preclinical models, including murine collagen-induced arthritis and conventional in vitro cultures, lack the complexity to fully recapitulate human disease mechanisms.\n\nMethods: Here, we describe the development of a three-dimensional (3D) RA bone–cartilage interface (BCI) organoid that integrates primary human mesenchymal stem cell-derived osteoblasts, peripheral blood mononuclear cell-derived osteoclasts and lymphocytes, immortalized human chondrocyte spheroids, and the RA synovial fibroblast cell line SW982.\n\nResults: Exposure to TNF-α, IL-1β, and TGF-β induced pro-inflammatory cytokines, matrix-degrading enzymes, and increased fibrotic gene expression, accompanied by histological and microCT evidence of bone dysregulation. Therapeutic testing showed that methotrexate, etanercept, and tofacitinib reduced cytokine production and pro-inflammatory gene expression but had limited impact on profibrotic gene expression.\n\nConclusions: This modular, human-derived RA BCI organoid reproduced key features of RA pathogenesis that can enable direct assessment of therapeutic mechanisms at the bone–cartilage–synovial interface. The RA BCI organoid provides a physiologically relevant, scalable platform for preclinical drug discovery and for identifying combination strategies that address both the inflammatory and fibrotic components of RA pathology.\n\nGraphical Abstract:\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s41232-026-00439-z.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biological Sciences, Seton Hall University, South Orange, NJ 07079 USA",
    "Department of Orthopaedics, Rutgers New Jersey Medical School, 90 Bergen Street, Suite 7300, Newark, NJ 07101 USA",
    "Scottsdale, AZ United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mary Adams"
    },
    {
      "affs": [
        1
      ],
      "name": "Christopher Grieg"
    },
    {
      "affs": [
        2
      ],
      "name": "Waldemar Gonsiorek"
    },
    {
      "affs": [
        1
      ],
      "name": "Charlene Wetterstrand"
    },
    {
      "affs": [
        1
      ],
      "name": "J. Patrick O’Connor"
    },
    {
      "affs": [
        0
      ],
      "name": "Jessica Cottrell"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/efjm7gmk4gs14.bib",
  "cited_by": 0,
  "doi": "10.1186/s41232-026-00439-z",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737601/",
  "id": "efjm7gmk4gs14",
  "issns": [
    "1880-9693",
    "1880-8190"
  ],
  "landing_url": "https://doi.org/10.1186/s41232-026-00439-z",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2745|Rheumatoid Arthritis Research and Therapies"
    ]
  ],
  "openalex": "W7201841764",
  "pdf_url": null,
  "pmcid": "PMC13737601",
  "pmid": "42983776",
  "published": "2026-08-08",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/efjm7gmk4gs14.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:44Z",
      "native_id": "PMC13737601",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s41232-026-00439-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Rheumatoid Arthritis Research and Therapies",
      "subfield": "general"
    }
  ],
  "title": "A human rheumatoid arthritis bone–cartilage interface organoid recapitulates bone, cartilage, and immune interactions",
  "title_text": "A human rheumatoid arthritis bone–cartilage interface organoid recapitulates bone, cartilage, and immune interactions",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:44Z",
  "url": "https://research.draconitic.com/paper/efjm7gmk4gs14",
  "venue": "Inflammation and Regeneration",
  "versions": []
}