title: Bone sialoprotein deficiency impairs osteoclastogenesis and mineral resorption in vitro.
abstract: Bone sialoprotein (BSP) and osteopontin (OPN) belong to the small integrin-binding ligand N-linked glycoprotein (SIBLING) family, whose members interact with bone cells and bone mineral. Previously, we showed that BSP knockout (BSP(-/-) ) mice have a higher bone mass than wild type (BSP(+/+) ) littermates, with very low bone-formation activity and reduced osteoclast surfaces and numbers. Here we report that approximately twofold fewer tartrate-resistant acid phosphatase (TRACP)-positive cells and approximately fourfold fewer osteoclasts form in BSP(-/-) compared with BSP(+/+) spleen cell cultures. BSP(-/-) preosteoclast cultures display impaired proliferation and enhanced apoptosis. Addition of RGD-containing proteins restores osteoclast number in BSP(-/-) cultures to BSP(+/+) levels. The expression of osteoclast-associated genes is markedly altered in BSP(-/-) osteoclasts, with reduced expression of cell adhesion and migration genes (αV integrin chain and OPN) and increased expression of resorptive enzymes (TRACP and cathepsin K). The migration of preosteoclasts and mature osteoclasts is impaired in the absence of BSP, but resorption pit assays on dentine slices show no significant difference in pit numbers between BSP(+/+) and BSP(-/-) osteoclasts. However, resorption of mineral-coated slides by BSP(-/-) osteoclasts is markedly impaired but is fully restored by coating the mineral substrate with hrBSP and partly restored by hrOPN coating. In conclusion, lack of BSP affects both osteoclast formation and activity, which is in accordance with in vivo findings. Our results also suggest at least some functional redundancy between BSP and OPN that remains to be clarified.
authors.affiliation: Université de Lyon, Saint-Etienne, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Boudiffa
authors.forename: Ndéye Marième
authors.initials: NM
authors.lastname: Wade-Gueye
authors.forename: Alain
authors.initials: A
authors.lastname: Guignandon
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vanden-Bossche
authors.forename: Odile
authors.initials: O
authors.lastname: Sabido
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.forename: Marie Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003804:Dentin / Q000378:metabolism; D017886:Durapatite / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D058574:Integrin-Binding Sialoprotein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008903:Minerals / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
chemical_list: D015415:Biomarkers; D058574:Integrin-Binding Sialoprotein; D008903:Minerals; D009842:Oligopeptides; D011994:Recombinant Proteins; D053495:Osteopontin; C047981:arginyl-glycyl-aspartic acid; D017886:Durapatite