{
  "abstract": "BackgroundAlcohol-induced osteonecrosis of the femoral head (AIONFH) is associated with impaired bone formation and increased bone cell apoptosis. This study investigated the role of osteoclast-derived exosomal miR-378a-3p and the FTO-mediated m6A pathway in AIONFH.MethodsRat bone marrow-derived macrophages (BMMs) were induced to form osteoclasts with or without ethanol. Exosomes were isolated, and differentially expressed miRNAs were identified by sequencing and RT-qPCR. The interaction between miR-378a-3p and FTO was examined using a dual-luciferase reporter assay. The effects of modified osteoclast-derived exosomes on BMSC osteogenic differentiation, apoptosis, FTO expression, and m6A levels were evaluated under ethanol exposure. An AIONFH rat model was used to assess the therapeutic effects of these exosomes in vivo.ResultsEthanol promoted osteoclast formation and reduced miR-378a-3p levels in osteoclast-derived exosomes. miR-378a-3p directly targeted the FTO 3′-UTR and reduced FTO expression. Under ethanol exposure, FTO expression increased, m6A levels decreased, osteogenic differentiation was inhibited, and apoptosis was increased. miR-378a-3p-enriched exosomes reversed these changes by reducing FTO expression, increasing m6A levels, promoting osteogenesis, and reducing apoptosis. In AIONFH rats, these exosomes improved trabecular bone structure, increased osteogenic marker expression, and reduced femoral head apoptosis. Exosomes with miR-378a-3p inhibition produced opposite effects.ConclusionOsteoclast-derived exosomal miR-378a-3p protects against alcohol-induced bone damage by targeting FTO and regulating m6A modification. The miR-378a-3p/FTO/m6A pathway may be a potential therapeutic target for AIONFH.",
  "abstract_shown": true,
  "affiliations": [
    "The First College of Clinical Medicine, Guangxi University of Chinese Medicine, Nanning, Guangxi, China",
    "Department of Orthopedics,The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning, Guangxi, China",
    "College of Traditional Chinese Medicine, Jinan University, Guangzhou, Guangdong, China",
    "The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China",
    "Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China",
    "Sanya Hospital of Traditional Chinese Medicine, Sanya, Hainan, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Canbin Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Jinfu Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Jinfu Liu"
    },
    {
      "affs": [
        3
      ],
      "name": "Dongfeng Chen"
    },
    {
      "affs": [
        4
      ],
      "name": "Donghui Guan"
    },
    {
      "affs": [
        5
      ],
      "name": "Liang Guo"
    },
    {
      "affs": [
        1
      ],
      "name": "Weiwei Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Qingyuan Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongcheng Tao"
    },
    {
      "affs": [
        0
      ],
      "name": "Chicheng Niu"
    },
    {
      "affs": [
        1
      ],
      "name": "Bin Sun"
    },
    {
      "affs": [
        4
      ],
      "name": "Jiang Shao"
    },
    {
      "affs": [
        1
      ],
      "name": "Ping Zeng"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c9f8asqykvbrr.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1975355",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fcell.2026.1975355/full",
  "id": "c9f8asqykvbrr",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://doi.org/10.3389/fcell.2026.1975355",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "1312|Extracellular vesicles in disease"
    ]
  ],
  "openalex": "W7223651980",
  "pdf_url": "https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2026.1975355/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/c9f8asqykvbrr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:47:30Z",
      "native_id": "6597b1116fe04c44b22359a67c7a0f4b",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fcell.2026.1975355"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Extracellular vesicles in disease",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Osteoclast-derived exosomal miR-378a-3p targets FTO-mediated m6A modification to promote osteogenesis and inhibit osteocyte apoptosis in alcohol-induced osteonecrosis of the femoral head",
  "title_text": "Osteoclast-derived exosomal miR-378a-3p targets FTO-mediated m6A modification to promote osteogenesis and inhibit osteocyte apoptosis in alcohol-induced osteonecrosis of the femoral head",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:30Z",
  "url": "https://research.draconitic.com/paper/c9f8asqykvbrr",
  "venue": "Frontiers in Cell and Developmental Biology",
  "versions": []
}