{
  "abstract": "Background and Aims. Hemophilia A (HA) is frequently associated with reduced bone mineral density and skeletal fragility, indicating a role for factor VIII (FVIII) in bone homeostasis. Emerging evidence suggests that FVIII may directly regulate osteoblast function. However, the underlying mechanisms remain poorly understood. This study investigated the effects of FVIII, von Willebrand factor (vWF), and the FVIII/vWF combination on osteoblast mineralization and explored FVIII-dependent changes in the osteoblast secretome. Methods. Primary osteoblast precursors were isolated from 3-week-old HA and wild-type (wt) mice and cultured under osteogenic conditions. During differentiation, the cultures were supplemented with increasing concentrations of recombinant FVIII (Nuwiq®), vWF, or the FVIII/vWF combination. Calcium deposition was assessed by Alizarin Red S staining. For secretome analysis, culture supernatants of HA and wt osteoblasts maintained for 48 hours were collected, and proteins were identified using Proteome Discoverer. Results. FVIII supplementation significantly increased calcium deposition in a dose-dependent manner in both HA and wt osteoblasts, with 10 ng/mL able to restore the mineralization deficit observed in untreated HA osteoblasts. In contrast, physiological concentrations of vWF selectively enhanced mineralization in HA osteoblasts, with no significant effect in wt cultures. Treatment with the FVIII/vWF complex increased calcium deposition exclusively in HA osteoblasts and only at hypophysiological concentrations (20 ng/mL FVIII – 1 mg/mL vWF). Secretome profiling revealed a reduced secretion of several proteins in HA compared with wt osteoblasts, while FVIII supplementation restored a wt-like secretome profile. Enrichment analysis identified pathways related to extracellular matrix organization, cell adhesion, wound healing, and skeletal development; among these, fibronectin and several collagen isoforms were particularly affected by FVIII deficiency. Conclusions. FVIII deficiency impairs osteoblast mineralization and secretory function, leading to altered ECM organization and reduced metabolic activity. These findings support a direct, non-hemostatic role for FVIII in osteoblast biology and indicate that VWF may modulate osteoblast activity under conditions of FVIII deficiency. Collectively, these data suggest that FVIII replacement therapy may contribute to improved bone integrity in patients with HA.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "name": "Baker Terkawi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/epwsvwqh4tx4v.bib",
  "cited_by": 0,
  "doi": null,
  "fulltext_url": "https://www.btvb.org/btvb/article/view/781",
  "id": "epwsvwqh4tx4v",
  "issns": [
    "2785-5309"
  ],
  "landing_url": "https://www.btvb.org/btvb/article/view/781",
  "language": "en",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC666-701"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": "PAGEPress Publications",
  "ris": "https://research.draconitic.com/paper/epwsvwqh4tx4v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:47:35Z",
      "native_id": "e9c2989e5c214cfea25556417ebc96b9",
      "source": "doaj",
      "url": "https://www.btvb.org/btvb/article/view/781"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC666-701",
      "subfield": "cardiovascular"
    }
  ],
  "title": "CO079 | FVIII DEFICIENCY COMPROMISES IN VITRO OSTEOBLASTS MINERALIZATION AND THEIR SECRETOME PROFILE",
  "title_text": "CO079 | FVIII DEFICIENCY COMPROMISES IN VITRO OSTEOBLASTS MINERALIZATION AND THEIR SECRETOME PROFILE",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:47:35Z",
  "url": "https://research.draconitic.com/paper/epwsvwqh4tx4v",
  "venue": "Bleeding, Thrombosis and Vascular Biology",
  "versions": []
}