Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis.
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.
Malaval
Luc
L
Institut National de Santé et de Recherche Médicale U890, IFR 143, Université Jean-Monnet, Saint-Etienne, F42023, France.
Wade-Guéye
Ndéyé Marième
NM
Boudiffa
Maya
M
Fei
Jia
J
Zirngibl
Ralph
R
Chen
Frieda
F
Laroche
Norbert
N
Roux
Jean-Paul
JP
Burt-Pichat
Brigitte
B
Duboeuf
François
F
Boivin
Georges
G
Jurdic
Pierre
P
Lafage-Proust
Marie-Hélène
MH
Amédée
Joëlle
J
Vico
Laurence
L
Rossant
Janet
J
Aubin
Jane E
JE
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
C506896:Spp1 protein, mouse; D053495:Osteopontin