{
  "abstract": "Traumatic heterotopic ossification (HO) is a debilitating complication of tendon injury, yet its pathogenic mechanisms remain elusive and effective preventive strategies are lacking. Here, we identify a glycometabolic-epigenetic axis that drives HO progression. Single-cell profiling and functional analyses reveal that hypoxic chondrocytes undergo glycolytic reprogramming, leading to lactate accumulation and transfer into tendon-derived mesenchymal stem cells (TD-MSCs) through MCT1. This metabolic coupling promotes P300-dependent histone H3 lysine 18 lactylation (H3K18la), activating osteogenic programs characterized by Col6a1, Zhx3, Lox and Vdr expression and thereby facilitating pathological endochondral ossification. Guided by this mechanism, we develop a tendon-adhesive hydrogel (GelHA-A485@Exos) that integrates mechanical repair with targeted epigenetic modulation. MSC-derived exosomes enable localized delivery of the P300 inhibitor A485, suppressing H3K18la and aberrant osteogenic activation, while the hydrogel scaffold enhances tendon regeneration. In vivo and in vitro studies demonstrate that GelHA-A485@Exos promotes tendon healing while preventing HO formation. Our findings establish metabolic-epigenetic communication as a central regulator of traumatic HO and provide a translational therapeutic strategy for its clinical prevention.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatric Orthopedic, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510515, China.",
    "Department of Sports Medicine, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510515, China.",
    "The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.",
    "Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.",
    "Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-Sen University, Guangzhou, Guangdong, 510000, China.",
    "Southern Medical University, Guangzhou, Guangdong Province, 510515, China.",
    "First Department of Neurology, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650031, China.",
    "Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province, 361004, China.",
    "Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Haoyang Feng"
    },
    {
      "affs": [
        0
      ],
      "name": "Kai Ang"
    },
    {
      "affs": [
        1
      ],
      "name": "Zengfa Deng"
    },
    {
      "affs": [
        2
      ],
      "name": "Chonghe Cui"
    },
    {
      "affs": [
        3
      ],
      "name": "Jialan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Nanfeng Huang"
    },
    {
      "affs": [
        4
      ],
      "name": "Yimei Feng"
    },
    {
      "affs": [
        5
      ],
      "name": "Jimei Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "Danlin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhen Kong"
    },
    {
      "affs": [
        7
      ],
      "name": "Zicheng Cai"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongjian Sun"
    },
    {
      "affs": [
        8
      ],
      "name": "Yusheng Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2rfyn56kcb8be.bib",
  "cited_by": 0,
  "doi": "10.1016/j.bioactmat.2026.10.006",
  "fulltext_url": "https://europepmc.org/articles/PMC13694767",
  "id": "2rfyn56kcb8be",
  "issns": [
    "2452-199X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42927122",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2745|Heterotopic Ossification and Related Conditions"
    ]
  ],
  "openalex": "W7221801461",
  "pdf_url": "https://europepmc.org/articles/PMC13694767?pdf=render",
  "pmcid": "PMC13694767",
  "pmid": "42927122",
  "published": "2026-10-14",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2rfyn56kcb8be.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:18Z",
      "native_id": "MED:42927122",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42927122"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2745|Heterotopic Ossification and Related Conditions",
      "subfield": "general"
    }
  ],
  "title": "Targeting the lactate/P300/H3K18la epigenetic pathway with a mechanoadaptive biomimetic hydrogel to suppress traumatic tendon heterotopic ossification.",
  "title_text": "Targeting the lactate/P300/H3K18la epigenetic pathway with a mechanoadaptive biomimetic hydrogel to suppress traumatic tendon heterotopic ossification.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:18Z",
  "url": "https://research.draconitic.com/paper/2rfyn56kcb8be",
  "venue": "Bioactive materials",
  "versions": []
}