{
  "abstract": "Background: Chemotherapy-induced bone loss (CIBL) is an important complication of anticancer treatment and is partly attributed to impaired osteogenic differentiation of bone marrow stromal/mesenchymal cells (BMSCs). Aloe-emodin (AE), a natural anthraquinone compound, has shown tissue-protective and anti-ferroptotic activities in chemotherapy-related organ injury. Its role in cisplatin (CDDP)-induced osteogenic impairment remains unclear.\n\nPurpose: To investigate whether ferroptosis contributes to CDDP-induced osteogenic suppression in BMSCs and whether AE protects against this process through a Yes-associated protein 1 (YAP1)-dependent mechanism.\n\nMethods: The anti-tumor effective concentration of CDDP was determined in 143B osteosarcoma cells. ST2 cells and primary mouse and human BMSCs were used to establish an in vitro model of CDDP-induced osteogenic impairment. Ferroptosis-related changes were assessed by Fe2⁺ accumulation, reactive oxygen species (ROS)/lipid peroxidation (LPO), and expression of related markers. Osteogenic differentiation was evaluated by alkaline phosphatase (AP) staining and osteogenic gene expression. RNA-seq, pharmacological inhibition, and Yap1 knockdown were used for mechanistic analysis.\n\nResults: CDDP concentrations that inhibited 143B cells also induced ferroptosis in ST2 cells, characterized by Fe2⁺ accumulation, increased ROS and LPO, decreased glutathione peroxidase 4 (GPX4), and impaired osteogenic differentiation. Ferrostatin-1 (Fer-1) alleviated ferroptotic stress and restored osteogenesis. Under co-treatment conditions, AE reduced Fe2⁺ overload, ROS and LPO, restored anti-ferroptotic defenses, and improved osteogenic differentiation in ST2 cells as well as in primary mouse and human BMSCs. AE did not protect 143B cells from CDDP cytotoxicity, but further enhanced CDDP-mediated growth inhibition. Mechanistically, CDDP suppressed YAP1 expression and nuclear localization, whereas AE restored YAP1 activity. Verteporfin and Yap1 knockdown abolished AE-mediated protection.\n\nConclusion: AE protects BMSCs from CDDP-induced ferroptotic osteogenic impairment through a YAP1-dependent mechanism without compromising the anti-osteosarcoma effect of CDDP in vitro.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, 402160, People’s Republic of China",
    "Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, People’s Republic of China",
    "Laboratory of Skeletal Development and Regeneration, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, People’s Republic of China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xiang Hong"
    },
    {
      "affs": [
        1
      ],
      "name": "Yufei Shao"
    },
    {
      "affs": [
        0
      ],
      "name": "Qing Sun"
    },
    {
      "affs": [
        2
      ],
      "name": "Jing Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengfan Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "Haoyang Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Xun Tang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xing Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaolin Tu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yujiao Liu",
      "orcid": "0000-0002-3946-0210"
    },
    {
      "affs": [
        0
      ],
      "name": "Gaohai Shao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4prntk63vctbk.bib",
  "cited_by": 0,
  "doi": "10.2147/dddt.s639514",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13729765/",
  "id": "4prntk63vctbk",
  "issns": [
    "1177-8881"
  ],
  "landing_url": "https://doi.org/10.2147/dddt.s639514",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1306|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W4416706284",
  "pdf_url": null,
  "pmcid": "PMC13729765",
  "pmid": "42979114",
  "published": "2026-10-30",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/4prntk63vctbk.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:22:30Z",
      "native_id": "PMC13729765",
      "source": "pmc",
      "url": "https://doi.org/10.2147/dddt.s639514"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Ferroptosis and cancer prognosis",
      "subfield": "oncology"
    }
  ],
  "title": "Aloe-Emodin Attenuates Cisplatin-Induced Ferroptotic Osteogenic Impairment in Bone Marrow Stromal Cells Through a YAP1-Dependent Mechanism",
  "title_text": "Aloe-Emodin Attenuates Cisplatin-Induced Ferroptotic Osteogenic Impairment in Bone Marrow Stromal Cells Through a YAP1-Dependent Mechanism",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:30Z",
  "url": "https://research.draconitic.com/paper/4prntk63vctbk",
  "venue": "Drug Design, Development and Therapy",
  "versions": []
}