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Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis.

Malaval L, Wade-Guéye NM, Boudiffa M, Fei J, Zirngibl R, Chen F, Laroche N, Roux JP, Burt-Pichat B, Duboeuf F, Boivin G, Jurdic P, Lafage-Proust MH, Amédée J, Vico L, Rossant J, Aubin JE - J. Exp. Med. (2008)

Bottom Line: BSP(-/-) hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal.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.

View Article: PubMed Central - PubMed

Affiliation: Institut National de Santé et de Recherche Médicale U890, IFR 143, Université Jean-Monnet, Saint-Etienne, F42023, France.

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.

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BSP−/− mice have higher trabecular bone density and lower bone turnover. (A) Trabecular bone volume in tibias of 4-mo-old mutant (−/−) and WT (+/+) mice of either sex as measured by three-dimensional μCT. (B) Three-dimensional reconstruction and trichrome-stained sections of +/+ and −/− female femur. Bar, 0.5 mm. (C) Histomorphometric parameters of bone formation and resorption in the femur of male and female mice, and the tibia of female +/+ and −/− 4-mo-old mice. (D) Histomorphometric assessment of osteoblast surface and osteoid mineralization in the tibia of 4-mo-old +/+ and −/− female mice. All values are the mean ± the SEM of 5 to 9 mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus matched +/+.
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fig2: BSP−/− mice have higher trabecular bone density and lower bone turnover. (A) Trabecular bone volume in tibias of 4-mo-old mutant (−/−) and WT (+/+) mice of either sex as measured by three-dimensional μCT. (B) Three-dimensional reconstruction and trichrome-stained sections of +/+ and −/− female femur. Bar, 0.5 mm. (C) Histomorphometric parameters of bone formation and resorption in the femur of male and female mice, and the tibia of female +/+ and −/− 4-mo-old mice. (D) Histomorphometric assessment of osteoblast surface and osteoid mineralization in the tibia of 4-mo-old +/+ and −/− female mice. All values are the mean ± the SEM of 5 to 9 mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus matched +/+.

Mentions: The trabecular bone volume (BV/TV) in long bones (Fig. 2, A and B) of BSP−/− male and female mice is ∼25–40% higher than in WT. This higher bone volume is associated with higher trabecular number (TbN) and lower trabecular separation (TbSp) in mutant versus WT bones, although trabecular thickness tends to be smaller in mutant mice (Table II). Double fluorochrome labeling revealed a very low bone formation activity in 4-mo-old male and female BSP−/− compared with WT mice (Fig. 2 C and Table II), both in terms of labeled surfaces (MS/BS) and apposition rate (MAR), resulting in a dramatically reduced bone formation rate (BFR). Low dynamic parameters of bone formation in BSP−/− mice correlate with reduced surfaces of cuboidal (plump) osteoblasts (Ob.S/BS; Fig. 2 D). In contrast, osteoid surface (OS/BS) and thickness (O.Th) are increased in BSP−/− mice, as well as mineralization lag time (MLT; Fig. 4 D), reflecting delayed primary mineralization. Osteoclast surfaces (Oc.S/BS) are reduced in mutant compared with WT femur of both sexes (Fig. 2 C). A similar phenotype is observed in tibia, where osteoclast numbers (N.Oc/B.Ar) were also found to be significantly reduced in BSP−/− mice (Fig. 2 C).


Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis.

Malaval L, Wade-Guéye NM, Boudiffa M, Fei J, Zirngibl R, Chen F, Laroche N, Roux JP, Burt-Pichat B, Duboeuf F, Boivin G, Jurdic P, Lafage-Proust MH, Amédée J, Vico L, Rossant J, Aubin JE - J. Exp. Med. (2008)

BSP−/− mice have higher trabecular bone density and lower bone turnover. (A) Trabecular bone volume in tibias of 4-mo-old mutant (−/−) and WT (+/+) mice of either sex as measured by three-dimensional μCT. (B) Three-dimensional reconstruction and trichrome-stained sections of +/+ and −/− female femur. Bar, 0.5 mm. (C) Histomorphometric parameters of bone formation and resorption in the femur of male and female mice, and the tibia of female +/+ and −/− 4-mo-old mice. (D) Histomorphometric assessment of osteoblast surface and osteoid mineralization in the tibia of 4-mo-old +/+ and −/− female mice. All values are the mean ± the SEM of 5 to 9 mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus matched +/+.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2373846&req=5

fig2: BSP−/− mice have higher trabecular bone density and lower bone turnover. (A) Trabecular bone volume in tibias of 4-mo-old mutant (−/−) and WT (+/+) mice of either sex as measured by three-dimensional μCT. (B) Three-dimensional reconstruction and trichrome-stained sections of +/+ and −/− female femur. Bar, 0.5 mm. (C) Histomorphometric parameters of bone formation and resorption in the femur of male and female mice, and the tibia of female +/+ and −/− 4-mo-old mice. (D) Histomorphometric assessment of osteoblast surface and osteoid mineralization in the tibia of 4-mo-old +/+ and −/− female mice. All values are the mean ± the SEM of 5 to 9 mice. *, P < 0.05; **, P < 0.01; ***, P < 0.001 versus matched +/+.
Mentions: The trabecular bone volume (BV/TV) in long bones (Fig. 2, A and B) of BSP−/− male and female mice is ∼25–40% higher than in WT. This higher bone volume is associated with higher trabecular number (TbN) and lower trabecular separation (TbSp) in mutant versus WT bones, although trabecular thickness tends to be smaller in mutant mice (Table II). Double fluorochrome labeling revealed a very low bone formation activity in 4-mo-old male and female BSP−/− compared with WT mice (Fig. 2 C and Table II), both in terms of labeled surfaces (MS/BS) and apposition rate (MAR), resulting in a dramatically reduced bone formation rate (BFR). Low dynamic parameters of bone formation in BSP−/− mice correlate with reduced surfaces of cuboidal (plump) osteoblasts (Ob.S/BS; Fig. 2 D). In contrast, osteoid surface (OS/BS) and thickness (O.Th) are increased in BSP−/− mice, as well as mineralization lag time (MLT; Fig. 4 D), reflecting delayed primary mineralization. Osteoclast surfaces (Oc.S/BS) are reduced in mutant compared with WT femur of both sexes (Fig. 2 C). A similar phenotype is observed in tibia, where osteoclast numbers (N.Oc/B.Ar) were also found to be significantly reduced in BSP−/− mice (Fig. 2 C).

Bottom Line: BSP(-/-) hematopoietic progenitors form fewer osteoclasts, but their resorptive activity on dentin is normal.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.

View Article: PubMed Central - PubMed

Affiliation: Institut National de Santé et de Recherche Médicale U890, IFR 143, Université Jean-Monnet, Saint-Etienne, F42023, France.

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.

Show MeSH
Related in: MedlinePlus