Published online May 5, 2008
doi:10.1084/jem.20071294
The Journal of Experimental Medicine
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Malaval et al.
Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis
Luc Malaval1,
Ndéyé Marième Wade-Guéye1,
Maya Boudiffa1,
Jia Fei1,
Ralph Zirngibl6,
Frieda Chen6,
Norbert Laroche1,
Jean-Paul Roux2,
Brigitte Burt-Pichat2,
François Duboeuf2,
Georges Boivin2,
Pierre Jurdic3,
Marie-Hélène Lafage-Proust1,
Joëlle Amédée4,
Laurence Vico1,
Janet Rossant5,6, and
Jane E. Aubin6
1 Institut National de la Santé et de la Recherche Médicale U890, IFR 143, Université Jean-Monnet, Saint-Etienne, F42023, France
2 Institut National de la Santé et de la Recherche Médicale U831, IFR 62, Université de Lyon, Lyon, F69008, France
3 Institut de Génomique Fonctionnelle de Lyon, Institut Fédératif Biosciences Gerland Lyon Sud, Université Lyon 1, Centre National de la Recherche Scientifique, INRA, Ecole Normale Supérieure, F69364 Lyon, France
4 Institut National de la Santé et de la Recherche Médicale U577, Université Victor Segalen, Bordeaux, F33076, France
5 Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario MG5 1X8, Canada
6 Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada
CORRESPONDENCE Jane E. Aubin: jane.aubin{at}utoronto.ca
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 (
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.
Abbreviations used: BFR, bone formation rate; BMD, bone mineral density; BSP, bone sialoprotein; DMP, dentin matrix protein; IBSP, integrin-binding sialoprotein; MEPE, matrix extracellular glycophosphoprotein; MLT, mineralization lag time; OPN, osteopontin; SIBLING, small, integrin-binding ligand N-linked glycoprotein; SPARC, secreted protein acidic and rich in cysteine; SPP, secreted phosphoprotein.
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Malaval, L., Wade-Gueye, N. M., Boudiffa, M., Fei, J., Zirngibl, R., Chen, F., Laroche, N., Roux, J.-P., Burt-Pichat, B., Duboeuf, F., Boivin, G., Jurdic, P., Lafage-Proust, M.-H., Amedee, J., Vico, L., Rossant, J., Aubin, J. E.
(2008). Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis. J. Cell Biol.
181: i14-i14
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