{
  "abstract": "Iron overload is a serious complication of thalassemia that affects various organ functions. Although iron chelators effectively alleviate iron overload, they have some adverse effects on bone structure. VIT-2763, an oral ferroportin-1 inhibitor, has been recently reported to reduce iron overload and improve ineffective erythropoiesis in β-thalassemia. Since iron is required for osteoblast and osteoclast functions, VIT-2763 was hypothesized to modulate bone metabolism. Herein, we used hemizygous βIVSII-654 knock-in thalassemic (B654) mice as a model of β-thalassemia with skeletal defects including trabecular bone loss and cortical thinning. At the cellular level, mRNA expression of bone formation-related genes (e.g., Runx2, ALP, osteocalcin) was upregulated in B654-derived primary osteoblasts. The mRNA expression of those bone formation-related genes was negatively correlated with ferroportin-1 expression in primary osteoblasts. In primary osteoclasts, the mRNA expression of mature osteoclast-specific genes was positively correlated with ferroportin-1 expression, suggesting an involvement of ferroportin-1 in regulating bone formation and resorption. We further showed that VIT-2763 effectively suppressed ferroportin-1 protein expression in both primary osteoblasts and osteoclasts. VIT-2763 decreased viability of primary osteoblasts without affecting osteoblast-specific gene expression and bone mineralization. Interestingly, VIT-2763 biphasically regulated osteoclastogenesis, particularly in early osteoclast differentiation, and attenuated osteoclast-mediated bone resorption in vitro. Quantitative analysis of three-dimensional (3D) osteoclastic hologram images found that VIT-2763 significantly altered cellular properties (e.g., mean refractive index) of primary osteoclasts in iron-loaded conditions. In conclusion, modulation of ferroportin-1 expression and cellular functions by VIT-2763 potentially inhibited osteoclast-mediated bone resorption. It may be a novel anti-resorptive agent for treating iron-induced osteopathy in β-thalassemia.",
  "abstract_shown": true,
  "affiliations": [
    "Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, Thailand",
    "Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand",
    "Physiology Division, Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand",
    "Research Center for Neuroscience, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand",
    "Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand",
    "Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand",
    "The Academy of Science, The Royal Society of Thailand, Bangkok, Thailand"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
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        0,
        1
      ],
      "name": "Ratchaneevan Aeimlapa"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Jarinthorn Teerapornpuntakit"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jirawan Thongbunchoo"
    },
    {
      "affs": [
        0
      ],
      "name": "Pathnaree Wattano"
    },
    {
      "affs": [
        3
      ],
      "name": "Jiraporn Panmanee"
    },
    {
      "affs": [
        4
      ],
      "name": "Saovaros Svasti"
    },
    {
      "affs": [
        0,
        1,
        5,
        6
      ],
      "name": "Narattaphol Charoenphandhu",
      "orcid": "0000-0002-2189-6542"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9gzyv66evfya2.bib",
  "cited_by": 0,
  "doi": "10.1038/s41420-026-03273-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714295/",
  "id": "9gzyv66evfya2",
  "issns": [
    "2058-7716"
  ],
  "landing_url": "https://doi.org/10.1038/s41420-026-03273-x",
  "language": "en",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2716|Hemoglobinopathies and Related Disorders"
    ]
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  "openalex": "W7171966070",
  "pdf_url": "https://www.nature.com/articles/s41420-026-03273-x_reference.pdf",
  "pmcid": "PMC13714295",
  "pmid": "42946715",
  "published": "2026-07-31",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/9gzyv66evfya2.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:21:49Z",
      "native_id": "PMC13714295",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41420-026-03273-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Hemoglobinopathies and Related Disorders",
      "subfield": "human-genetics"
    }
  ],
  "title": "VIT-2763, a ferroportin-1 inhibitor, modulates osteoblast and osteoclast functions in hemizygous βIVSII-654 knock-in thalassemic mice with osteopenia",
  "title_text": "VIT-2763, a ferroportin-1 inhibitor, modulates osteoblast and osteoclast functions in hemizygous βIVSII-654 knock-in thalassemic mice with osteopenia",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:49Z",
  "url": "https://research.draconitic.com/paper/9gzyv66evfya2",
  "venue": "Cell Death Discovery",
  "versions": []
}