{
  "abstract": "Renal osteodystrophy is a debilitating complication of chronic kidney disease characterized by deteriorated bone microarchitecture and impaired bone formation, leading to increased fracture risk. Despite the pressing need for anabolic therapies, the cellular mechanisms by which uremic stress compromises osteoprogenitor function remain poorly defined. Here, metabolomic profiling of renal osteodystrophy patient cohorts revealed a profound depletion of circulating betaine. We show that betaine supplementation not only rescued the osteogenic differentiation of bone marrow-derived mesenchymal stem cells challenged with the uremic toxin indoxyl sulfate but also ameliorated skeletal deterioration in a rat model of chronic kidney disease. Mechanistically, we demonstrated that indoxyl sulfate triggered ferroptosis in bone marrow-derived mesenchymal stem cells-characterized by iron-dependent lipid peroxidation and aberrant HMOX1 up-regulation-thereby arresting osteogenesis. Betaine mitigates this ferroptotic stress through a novel post-transcriptional mechanism. Specifically, betaine down-regulated the RNA-binding protein hnRNP A1, preventing the recruitment of the CNOT1 deadenylase complex. This inhibition stabilized Abcg1 mRNA, leading to restored ABCG1 expression. Functional perturbation studies confirmed that the ABCG1-HMOX1 axis was indispensable for the anti-ferroptotic and osteoprotective effects of betaine. Collectively, our findings delineate a Betaine-hnRNP A1/CNOT1-ABCG1-HMOX1 signaling cascade that links metabolic deficiency to ferroptosis-driven osteogenic failure, positioning betaine as a promising anabolic therapeutic strategy for renal osteodystrophy.",
  "abstract_shown": true,
  "affiliations": [
    "Departments of Nephrology, Orthopedics, Urological Metabolism and Immunoecology Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.",
    "Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing 400016, China.",
    "Department of Pharmacy, Beijing Anzhen Nanchong Hospital, Capital Medical University & Nanchong Central Hospital, Nanchong, Sichuan 637000, China.",
    "Department of Pharmacy, The Second Clinical Medical College of North Sichuan Medical College, Nanchong, Sichuan 637000, China.",
    "Nanchong Key Laboratory of Individualized Drug Therapy, Nanchong, Sichuan 637000, China.",
    "Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.",
    "National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan 410008, China.",
    "Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing 400016, China.",
    "The Children's Hospital of Chongqing Medical University, Chongqing 400014, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinhang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Xie"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Wenyan Ren"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Qing Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiming Pang"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Wenting Liu"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Xin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Bin He"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Dongmei He"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Xinyue Wan"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Jia Liu"
    },
    {
      "affs": [
        1,
        8
      ],
      "name": "Jie Cai"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Baicheng He"
    },
    {
      "affs": [
        0
      ],
      "name": "Wei Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Fang He"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a21fm9vgxsjvt.bib",
  "cited_by": 0,
  "doi": "10.1016/j.gendis.2026.102444",
  "fulltext_url": "https://europepmc.org/articles/PMC13679308",
  "id": "a21fm9vgxsjvt",
  "issns": [
    "2352-4820",
    "2352-3042"
  ],
  "landing_url": "https://europepmc.org/article/MED/42899164",
  "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": [
    [
      "openalex",
      "2727|Parathyroid Disorders and Treatments"
    ]
  ],
  "openalex": "W7208718586",
  "pdf_url": "https://europepmc.org/articles/PMC13679308?pdf=render",
  "pmcid": "PMC13679308",
  "pmid": "42899164",
  "published": "2026-09-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/a21fm9vgxsjvt.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42899164",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42899164"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2727|Parathyroid Disorders and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Betaine alleviates renal osteodystrophy by stabilizing ABCG1 mRNA to inhibit HMOX1-mediated ferroptosis in BMSCs.",
  "title_text": "Betaine alleviates renal osteodystrophy by stabilizing ABCG1 mRNA to inhibit HMOX1-mediated ferroptosis in BMSCs.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/a21fm9vgxsjvt",
  "venue": "Genes & diseases",
  "versions": []
}