title: Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis.
abstract: Bone sialoprotein (BSP) and osteopontin (OPN) are both highly expressed in bone, but their functional specificities are unknown. OPN knockout (-/-) mice do not lose bone in a model of hindlimb disuse (tail suspension), showing the importance of OPN in bone remodeling. We report that BSP(-/-) mice are viable and breed normally, but their weight and size are lower than wild-type (WT) mice. Bone is undermineralized in fetuses and young adults, but not in older (> or =12 mo) BSP(-/-) mice. At 4 mo, BSP(-/-) mice display thinner cortical bones than WT, but greater trabecular bone volume with very low bone formation rate, which indicates reduced resorption, as confirmed by lower osteoclast surfaces. Although the frequency of total colonies and committed osteoblast colonies is the same, fewer mineralized colonies expressing decreased levels of osteoblast markers form in BSP(-/-) versus WT bone marrow stromal cultures. BSP(-/-) hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal. Tail-suspended BSP(-/-) mice lose bone in hindlimbs, as expected. In conclusion, BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation. It does not, however, prevent the bone loss resulting from loss of mechanical stimulation, a phenotype that is clearly different from OPN(-/-) mice.
authors.affiliation: Institut National de Santé et de Recherche Médicale U890, IFR 143, Université Jean-Monnet, Saint-Etienne, F42023, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Malaval
authors.forename: Ndéyé Marième
authors.initials: NM
authors.lastname: Wade-Guéye
authors.forename: Maya
authors.initials: M
authors.lastname: Boudiffa
authors.forename: Jia
authors.initials: J
authors.lastname: Fei
authors.forename: Ralph
authors.initials: R
authors.lastname: Zirngibl
authors.forename: Frieda
authors.initials: F
authors.lastname: Chen
authors.forename: Norbert
authors.initials: N
authors.lastname: Laroche
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Roux
authors.forename: Brigitte
authors.initials: B
authors.lastname: Burt-Pichat
authors.forename: François
authors.initials: F
authors.lastname: Duboeuf
authors.forename: Georges
authors.initials: G
authors.lastname: Boivin
authors.forename: Pierre
authors.initials: P
authors.lastname: Jurdic
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
authors.forename: Joëlle
authors.initials: J
authors.lastname: Amédée
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
authors.forename: Janet
authors.initials: J
authors.lastname: Rossant
authors.forename: Jane E
authors.initials: JE
authors.lastname: Aubin
mesh_terms: D000818:Animals; D015519:Bone Density; D001846:Bone Development; D001862:Bone Resorption / Q000503:physiopathology; D002113:Calcification, Physiologic; D017353:Gene Deletion; D006614:Hindlimb; D051379:Mice; D008815:Mice, Inbred Strains; D010010:Osteoclasts / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D053495:Osteopontin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015183:Restriction Mapping; D016474:Weight-Bearing
chemical_list: C506896:Spp1 protein, mouse; D053495:Osteopontin