title: Osteoclast formation is strongly reduced both in vivo and in vitro in the absence of CD47/SIRPalpha-interaction.
abstract: Physical interaction between the cell surface receptors CD47 and signal regulatory protein alpha (SIRPalpha) was reported to regulate cell migration, phagocytosis, cytokine production, and macrophage fusion. However, it is unclear if the CD47/SIRPalpha-interaction can also regulate macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-stimulated formation of osteoclasts. Here, we show that functional blocking antibodies to either CD47 or SIRPalpha strongly reduced formation of multinucleated tartrate-resistant acid phosphatase (TRAP)+ osteoclasts in cultures of murine hematopoietic cells, stimulated in vitro by M-CSF and RANKL. In addition, the numbers of osteoclasts formed in M-CSF/RANKL-stimulated bone marrow macrophage cultures from CD47-/- mice were strongly reduced, and bones of CD47-/- mice exhibited significantly reduced osteoclast numbers, as compared with wild-type controls. We conclude that the CD47/SIRPalpha interaction is important for M-CSF/RANKL-stimulated osteoclast formation both in vivo and in vitro, and that absence of CD47 results in decreased numbers of osteoclasts in CD47-/- mice.
authors.affiliation: Department of Odontology, Section for Oral Cell Biology, Umeå University, Sweden. pernilla.lundberg@odont.umu.se
authors.forename: Pernilla
authors.initials: P
authors.lastname: Lundberg
authors.forename: Cecilia
authors.initials: C
authors.lastname: Koskinen
authors.forename: Paul A
authors.initials: PA
authors.lastname: Baldock
authors.forename: Hanna
authors.initials: H
authors.lastname: Löthgren
authors.forename: Asa
authors.initials: A
authors.lastname: Stenberg
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis / Q000502:physiology*; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D051928:CD47 Antigen; C497895:Cd47 protein, mouse; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic