{
  "abstract": "Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for H3K27 trimethylation, has emerged as a potential therapeutic target in osteoarthritis (OA). However, its contribution to the multicellular mechanisms driving joint degeneration and pain remains poorly understood. Here, we investigated the effects of pharmacological EZH2 inhibition in a pain-relevant murine OA model and explored its cellular and molecular consequences across OA-associated cell populations. OA was induced in mice by intra-articular monosodium iodoacetate (MIA) injection followed by local administration of the EZH2 inhibitor EPZ-6438. Joint pathology and pain-related behaviors were assessed by histological and functional analyses. Mechanistic studies were performed in primary human OA fibroblast-like synoviocytes and bone marrow-derived cells using targeted gene expression analyses, proteomics and ChIP-seq approaches. EZH2 inhibition reduced cartilage damage, synovial inflammation and pain-related behavioral alterations in vivo. In OA synoviocytes, EPZ-6438 decreased the expression of inflammatory, catabolic and pain-associated mediators while promoting autophagy-related responses. Proteomic and ChIP-seq analyses revealed EZH2-dependent regulation of inflammatory pathways, cellular homeostasis and neuronal-associated processes, including axon guidance-related pathways. ChIP-seq further identified inflammation-dependent EZH2 recruitment to promoters of neurodevelopmental regulators, including PAX6, suggesting a potential contribution of EZH2 to neuronal-associated mechanisms in OA. In addition, EZH2 inhibition reduced macrophage inflammatory activation and osteoclast differentiation. Together, these findings identify EZH2 as a candidate epigenetic regulator linking inflammatory, neuroimmune and osteoimmune pathways across the osteoarthritic joint. Targeting EZH2 may represent a therapeutic strategy to simultaneously modulate joint inflammation, remodeling and pain-associated pathways.",
  "abstract_shown": true,
  "affiliations": [
    "UR7451 BIOCONNECT, Université de Caen Normandie, Caen, F-14000, France.",
    "US EMerode, PROTEOGEN, Université de Caen Normandie, Caen, 14000, France.",
    "Institut Blood and Brain @Caen-Normandie (BB@C), UMR-S U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Normandie Univ, UNICAEN, INSERM, GIP Cyceron, 14000, Caen, France.",
    "Regenerative Medicine and Skeleton (RMeS), UMR 1229, INSERM, Nantes Université, CHU Nantes, Oniris, Nantes, 44000, France.",
    "Service de Chirurgie Orthopédique, Hôpital Privé St Martin, 14000, Caen, France.",
    "CRCI2NA, CNRS 6075, Inserm 1307, Nantes Université, Université d'Angers, Nantes, F-44000, France.",
    "UR7451 BIOCONNECT, Université de Caen Normandie, Caen, F-14000, France. catherine.bauge@unicaen.fr."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sybille Brochard"
    },
    {
      "affs": [
        0
      ],
      "name": "Alison Vanlaeys"
    },
    {
      "affs": [
        0
      ],
      "name": "Mahdia Taieb"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabelle Richard"
    },
    {
      "affs": [
        0
      ],
      "name": "Juliette Aury-Landas"
    },
    {
      "affs": [
        1
      ],
      "name": "Benoit Bernay"
    },
    {
      "affs": [
        1
      ],
      "name": "Julien Pontin"
    },
    {
      "affs": [
        2
      ],
      "name": "Celia Seillier"
    },
    {
      "affs": [
        3
      ],
      "name": "Nina Bon"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Baptiste Picart"
    },
    {
      "affs": [
        5
      ],
      "name": "Claire Pecqueur"
    },
    {
      "affs": [
        2
      ],
      "name": "Olivier Toutirais"
    },
    {
      "affs": [
        3
      ],
      "name": "Claire Vinatier"
    },
    {
      "affs": [
        3
      ],
      "name": "Jérôme Guicheux"
    },
    {
      "affs": [
        2
      ],
      "name": "Eric Maubert"
    },
    {
      "affs": [
        2
      ],
      "name": "Véronique Agin"
    },
    {
      "affs": [
        0
      ],
      "name": "Karim Boumediene"
    },
    {
      "affs": [
        6
      ],
      "name": "Catherine Bauge",
      "orcid": "0000-0001-5642-998X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e2zhcsajtt5yz.bib",
  "cited_by": 0,
  "doi": "10.1186/s43556-026-00643-w",
  "fulltext_url": "https://europepmc.org/articles/PMC13694607",
  "id": "e2zhcsajtt5yz",
  "issns": [
    "2662-8651"
  ],
  "landing_url": "https://europepmc.org/article/MED/42920051",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2745|Osteoarthritis Treatment and Mechanisms"
    ]
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  "openalex": "W7223406371",
  "pdf_url": "https://europepmc.org/articles/PMC13694607?pdf=render",
  "pmcid": "PMC13694607",
  "pmid": "42920051",
  "published": "2026-10-24",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/e2zhcsajtt5yz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42920051",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42920051"
    },
    {
      "first_seen": "2026-10-30T13:45:36Z",
      "native_id": "b2b8ca6d3e264c8d86bc8a2ba082fd8d",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s43556-026-00643-w"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Osteoarthritis Treatment and Mechanisms",
      "subfield": "general"
    }
  ],
  "title": "EZH2 coordinates inflammatory and pain-associated pathways across joint compartments in osteoarthritis.",
  "title_text": "EZH2 coordinates inflammatory and pain-associated pathways across joint compartments in osteoarthritis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:36Z",
  "url": "https://research.draconitic.com/paper/e2zhcsajtt5yz",
  "venue": "Molecular biomedicine",
  "versions": []
}