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Hypoxia-reperfusion affects osteogenic lineage and promotes sickle cell bone disease.
Dalle Carbonare, Luca; Matte', Alessandro; Valenti, Maria Teresa; Siciliano, Angela; Mori, Antonio; Schweiger, Vittorio; Zampieri, Gino; Perbellini, Luigi; De Franceschi, Lucia.
Afiliação
  • Dalle Carbonare L; Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;
  • Matte' A; Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;
  • Valenti MT; Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;
  • Siciliano A; Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;
  • Mori A; Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;
  • Schweiger V; Department of Surgical Science, Anesthesiology, Intensive Care and Pain Therapy Center, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;
  • Zampieri G; Advanced Consulting Engineering AC&E, Verona, Italy; and.
  • Perbellini L; Department of Public Health and Community Medicine, University of Verona, Verona, Italy.
  • De Franceschi L; Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy;
Blood ; 126(20): 2320-8, 2015 Nov 12.
Article em En | MEDLINE | ID: mdl-26330244
ABSTRACT
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder, characterized by severe organ complication. Sickle bone disease (SBD) affects a large part of the SCD patient population, and its pathogenesis has been only partially investigated. Here, we studied bone homeostasis in a humanized mouse model for SCD. Under normoxia, SCD mice display bone loss and bone impairment, with increased osteoclast and reduced osteoblast activity. Hypoxia/reperfusion (H/R) stress, mimicking acute vaso-occlusive crises (VOCs), increased bone turnover, osteoclast activity (RankL), and osteoclast recruitment (Rank) with upregulation of IL-6 as proresorptive cytokine. This was associated with further suppression of osteogenic lineage (Runx2, Sparc). To interfere with the development of SBD, zoledronic acid (Zol), a potent inhibitor of osteoclast activity/osteoclastogenesis and promoter of osteogenic lineage, was used in H/R-exposed mice. Zol markedly inhibited osteoclast activity and recruitment, promoting osteogenic lineage. The recurrent H/R stress further worsened bone structure, increased bone turnover, depressed osteoblastogenesis (Runx2, Sparc), and increased both osteoclast activity (RankL, Cathepsin k) and osteoclast recruitment (Rank) in SCD mice compared with either normoxic or single-H/R-episode SCD mice. Zol used before recurrent VOCs prevented bone impairment and promoted osteogenic lineage. Our findings support the view that SBD is related to osteoblast impairment, and increased osteoclast activity resulted from local hypoxia, oxidative stress, and the release of proresorptive cytokine such as IL-6. Zol might act on both the osteoclast and osteoblast compartments as multimodal therapy to prevent SBD.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoclastos / Doenças Ósseas / Traumatismo por Reperfusão / Anemia Falciforme Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoclastos / Doenças Ósseas / Traumatismo por Reperfusão / Anemia Falciforme Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2015 Tipo de documento: Article