{
  "abstract": "Introduction: The accumulation of senescent chondrocytes (SEC) beyond the body’s tolerance capacity is a key contributor to osteoarthritis (OA) pathogenesis. Metformin (Met), a first-line oral medication for type 2 diabetes, has shown therapeutic potential in various diseases. This study aims to explore the therapeutic effects and underlying mechanisms of Met in OA.\n\nMethods: Cellular senescence was induced in immortalized human chondrocytes using doxorubicin (Dox), confirmed by β-galactosidase staining and western blotting. The effects of Met on SEC viability, mitochondrial membrane potential, and apoptosis were assessed. Protein expression and interactions were analyzed by western blot and live-cell fluorescence resonance energy transfer (FRET) analysis.\n\nResults: Met promoted death of SEC and reduced mitochondrial membrane potential, inducing caspase- and reactive oxygen species (ROS)-dependent apoptosis. Met upregulated Bak and Bim expression, downregulated Mcl-1, and activated Caspase-3, Caspase-8, and Caspase-9, leading to PARP cleavage. FRET analysis revealed that Met disrupted Mcl-1/Bak and Bcl-xL/Bak binding while facilitating Bim-Bak interaction, promoting Bak dimerization.\n\nDiscussion: This study provides the first evidence that Met induces apoptosis of SEC by reducing Mcl-1-Bak and Bcl-xL-Bak interactions while enhancing Bim-Bak binding, suggesting a novel therapeutic strategy for OA by targeting senescent chondrocytes through mitochondrial apoptosis pathways.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology, The First Affiliated Hospital of Shantou University Medical College",
    "Department of Pain Management, The Second Affiliated Hospital of Shantou University Medical College"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Biying Feng"
    },
    {
      "affs": [
        1
      ],
      "name": "Longzhou Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yueyang Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Guihao Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b4jxe7fk1exhn.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1944776",
  "fulltext_url": null,
  "id": "b4jxe7fk1exhn",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1944776/full",
  "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": "W7224115679",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/b4jxe7fk1exhn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1944776",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1944776/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Metformin promotes apoptosis of senescent chondrocytes by disrupting the Bcl-xL/Mcl-1–Bak interaction",
  "title_text": "Metformin promotes apoptosis of senescent chondrocytes by disrupting the Bcl-xL/Mcl-1–Bak interaction",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/b4jxe7fk1exhn",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}