Sustained Autocrine Induction and Impaired Negative Feedback of Osteoclastogenesis in CD14(+) Cells of Giant Cell Tumor of Bone (Articolo in rivista)

Type
Label
  • Sustained Autocrine Induction and Impaired Negative Feedback of Osteoclastogenesis in CD14(+) Cells of Giant Cell Tumor of Bone (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.ajpath.2012.12.021 (literal)
Alternative label
  • Avnet S; Salerno M; Zini N; Alberghini M; Gibellini D; Baldini N (2013)
    Sustained Autocrine Induction and Impaired Negative Feedback of Osteoclastogenesis in CD14(+) Cells of Giant Cell Tumor of Bone
    in The American journal of pathology (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Avnet S; Salerno M; Zini N; Alberghini M; Gibellini D; Baldini N (literal)
Pagina inizio
  • 1357 (literal)
Pagina fine
  • 1366 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 182 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 10 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 4 (literal)
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Laboratory for Orthopaedic Pathophysiology and Regenerative Medicine; Institute of Molecular Genetics,National Research Council of Italy,Unit of Bologna; Department of Surgical Pathology, and First Orthopaedic Surgical Unit, Istituto Ortopedico Rizzoli; Departments of Specialized, Experimental and Diagnostic Medicine and Biomedical and Neuromotor Sciences,University of Bologna, Bologna, Italy (literal)
Titolo
  • Sustained Autocrine Induction and Impaired Negative Feedback of Osteoclastogenesis in CD14(+) Cells of Giant Cell Tumor of Bone (literal)
Abstract
  • Giant cell tumor (GCT) of bone is a histologically benign osteolytic tumor featuring prominent osteoclast-like giant cells, mononuclear osteoclast precursors, and spindle-shaped stromal cells (SCs). Thus far, most studies have identified SCs as truly transformed elements that are responsible for sustained giant cell formation via receptor activator of NF-kappa B ligand (RANKL) paracrine induction. However, we have previously shown that SCs are hyperplastic, rather than neoplastic, and able to induce giant cell formation similar to that of normal mesenchymal SCs; we hypothesized that other cell subsets of GCTs might be primarily relevant for the pathogenesis. In this study, we show that the non-proliferating CD14(+) cells of GCTs, exhibiting typical monoblast Lineage features, secrete high amounts of RANKL, thereby activating a RANKL/RANK autocrine loop that determines sustained giant cell formation. Moreover, these cells also lack adequate negative feedback control of the RANKL signaling pathway, as determined by endogenous interferon beta. These data demonstrate that CD14(+) cells of GCTs are abnormally stimulated to limitless differentiation into multinucleated giant cells and provide useful suggestions for the development of novel therapies. (literal)
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