{
  "abstract": "Steroid-induced osteonecrosis of the femoral head (SONFH) is a progressive orthopedic disorder characterized by an imbalance between bone resorption and bone formation. Although receptor activator of nuclear factor kappa-B ligand (RANKL) blockers are known to suppress osteoclast activity, whether they also promote osteogenesis and the underlying molecular mechanisms remain poorly understood. In this study, we investigated whether osteoprotegerin-Fc (OPG-Fc) exerts osteoprotective effects in SONFH and whether wingless-type MMTV integration site family, member 5A (WNT5A) signaling is involved. A rat SONFH model was established using lipopolysaccharide (LPS) combined with methylprednisolone sodium succinate (MPS), and bone marrow mesenchymal stem cells (BMSCs) were cultured under glucocorticoid-containing conditions. OPG-Fc, the WNT5A antagonist box5, and Wnt5a knockdown were used, and analyses included micro-computed tomography (micro-CT), histological staining, transcriptome sequencing, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting. Our results demonstrated that OPG-Fc significantly improved bone trabecular microarchitecture, reduced empty lacunae and tartrate-resistant acid phosphatase (TRAP)-positive cells, and increased cartilage thickness in vivo. In vitro, OPG-Fc promoted osteogenic differentiation while inhibiting adipogenic differentiation of BMSCs. Transcriptome and protein analyses revealed significantly higher WNT5A expression following OPG-Fc treatment. Importantly, pharmacological blockade of WNT5A with box5 and Wnt5a knockdown partially attenuated OPG-Fc-associated pro-osteogenic effects, whereas box5 had limited effects on anti-resorptive marker changes. These findings suggest that OPG-Fc exerts dual protective actions in SONFH by suppressing bone resorption and enhancing osteogenic differentiation in association with WNT5A-related signaling. This study provides new mechanistic insights into RANKL blockade therapy and offers a potential molecular target for early intervention in SONFH.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, The 920th Hospital of Joint Logistics Support Force of PLA, Kunming 650032 Guangzhou 510010 China",
    "Department of Orthopedics, General Hospital of Southern Theater Command of PLA Guangzhou 510010 China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Wei Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Zeyu Dai"
    },
    {
      "affs": [
        0
      ],
      "name": "Chaobo Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yongqing Xu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/41rtwq35bhf13.bib",
  "cited_by": 0,
  "doi": "10.4062/biomolther.2026.087",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725003/",
  "id": "41rtwq35bhf13",
  "issns": [
    "1976-9148",
    "2005-4483"
  ],
  "landing_url": "https://doi.org/10.4062/biomolther.2026.087",
  "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 Article"
    ],
    [
      "openalex",
      "2732|Bone and Joint Diseases"
    ]
  ],
  "openalex": "W7224284602",
  "pdf_url": null,
  "pmcid": "PMC13725003",
  "pmid": "42952216",
  "published": "2026-11-01",
  "publisher": "Korean Society of Applied Pharmacology",
  "ris": "https://research.draconitic.com/paper/41rtwq35bhf13.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:23:28Z",
      "native_id": "PMC13725003",
      "source": "pmc",
      "url": "https://doi.org/10.4062/biomolther.2026.087"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2732|Bone and Joint Diseases",
      "subfield": "surgery"
    }
  ],
  "title": "WNT5A-Associated Osteogenic Enhancement Contributes to the Protective Effects of OPG-Fc in Glucocorticoid-Associated Femoral Head Osteonecrosis",
  "title_text": "WNT5A-Associated Osteogenic Enhancement Contributes to the Protective Effects of OPG-Fc in Glucocorticoid-Associated Femoral Head Osteonecrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:22Z",
  "url": "https://research.draconitic.com/paper/41rtwq35bhf13",
  "venue": "Biomolecules & Therapeutics",
  "versions": []
}