title: Dendritic cell-mediated in vivo bone resorption.
abstract: Osteoclasts are resident cells of the bone that are primarily involved in the physiological and pathological remodeling of this tissue. Mature osteoclasts are multinucleated giant cells that are generated from the fusion of circulating precursors originating from the monocyte/macrophage lineage. During inflammatory bone conditions in vivo, de novo osteoclastogenesis is observed but it is currently unknown whether, besides increased osteoclast differentiation from undifferentiated precursors, other cell types can generate a multinucleated giant cell phenotype with bone resorbing activity. In this study, an animal model of calvaria-induced aseptic osteolysis was used to analyze possible bone resorption capabilities of dendritic cells (DCs). We determined by FACS analysis and confocal microscopy that injected GFP-labeled immature DCs were readily recruited to the site of osteolysis. Upon recruitment, the cathepsin K-positive DCs were observed in bone-resorbing pits. Additionally, chromosomal painting identified nuclei from female DCs, previously injected into a male recipient, among the nuclei of giant cells at sites of osteolysis. Finally, osteolysis was also observed upon recruitment of CD11c-GFP conventional DCs in Csf1r(-/-) mice, which exhibit a severe depletion of resident osteoclasts and tissue macrophages. Altogether, our analysis indicates that DCs may have an important role in bone resorption associated with various inflammatory diseases.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, New York, NY 10461, USA.
authors.forename: Radhashree
authors.initials: R
authors.lastname: Maitra
authors.forename: Antonia
authors.initials: A
authors.lastname: Follenzi
authors.forename: Arash
authors.initials: A
authors.lastname: Yaghoobian
authors.forename: Cristina
authors.initials: C
authors.lastname: Montagna
authors.forename: Simone
authors.initials: S
authors.lastname: Merlin
authors.forename: Elvira S
authors.initials: ES
authors.lastname: Cannizzo
authors.forename: John A
authors.initials: JA
authors.lastname: Hardin
authors.forename: Neil
authors.initials: N
authors.lastname: Cobelli
authors.forename: E Richard
authors.initials: ER
authors.lastname: Stanley
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000473:pathology; D001862:Bone Resorption / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000276:immunology / Q000473:pathology; D010014:Osteolysis / Q000276:immunology / Q000473:pathology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D012886:Skull / Q000276:immunology / Q000473:pathology; D014161:Transduction, Genetic
chemical_list: D016186:Receptor, Macrophage Colony-Stimulating Factor