Limits...
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: 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.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

In vivo and in vitro effects of BSP deletion on osteoblast marker expression. (A) Real-time PCR analysis of osteocalcin (OCN), OPN, tissue nonspecific alkaline phosphatase (ALP), type I collagen (COLL I), osterix (OSX), osteoprotegerin (OPG), and receptor-activator of NF-κB (RANKL) mRNA expression in femurs of 4-mo-old male BSP−/− mice. Values are the mean ± the SEM of 3–4 mice (except for OSX) normalized to housekeeping gene L32 and expressed as the percentage of WT levels. (B) Time course of expression of COLL I, OCN, OSX, and OPN mRNA as assessed by real-time PCR in bone marrow cultures of WT (empty symbols) and mutant (black symbols) mice, grown in osteogenic conditions. Values were normalized to time-matched levels of the housekeeping gene L32. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 versus matched WT.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: In vivo and in vitro effects of BSP deletion on osteoblast marker expression. (A) Real-time PCR analysis of osteocalcin (OCN), OPN, tissue nonspecific alkaline phosphatase (ALP), type I collagen (COLL I), osterix (OSX), osteoprotegerin (OPG), and receptor-activator of NF-κB (RANKL) mRNA expression in femurs of 4-mo-old male BSP−/− mice. Values are the mean ± the SEM of 3–4 mice (except for OSX) normalized to housekeeping gene L32 and expressed as the percentage of WT levels. (B) Time course of expression of COLL I, OCN, OSX, and OPN mRNA as assessed by real-time PCR in bone marrow cultures of WT (empty symbols) and mutant (black symbols) mice, grown in osteogenic conditions. Values were normalized to time-matched levels of the housekeeping gene L32. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 versus matched WT.

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)

In vivo and in vitro effects of BSP deletion on osteoblast marker expression. (A) Real-time PCR analysis of osteocalcin (OCN), OPN, tissue nonspecific alkaline phosphatase (ALP), type I collagen (COLL I), osterix (OSX), osteoprotegerin (OPG), and receptor-activator of NF-κB (RANKL) mRNA expression in femurs of 4-mo-old male BSP−/− mice. Values are the mean ± the SEM of 3–4 mice (except for OSX) normalized to housekeeping gene L32 and expressed as the percentage of WT levels. (B) Time course of expression of COLL I, OCN, OSX, and OPN mRNA as assessed by real-time PCR in bone marrow cultures of WT (empty symbols) and mutant (black symbols) mice, grown in osteogenic conditions. Values were normalized to time-matched levels of the housekeeping gene L32. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 versus matched WT.
© Copyright Policy
Related In: Results  -  Collection

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

fig4: In vivo and in vitro effects of BSP deletion on osteoblast marker expression. (A) Real-time PCR analysis of osteocalcin (OCN), OPN, tissue nonspecific alkaline phosphatase (ALP), type I collagen (COLL I), osterix (OSX), osteoprotegerin (OPG), and receptor-activator of NF-κB (RANKL) mRNA expression in femurs of 4-mo-old male BSP−/− mice. Values are the mean ± the SEM of 3–4 mice (except for OSX) normalized to housekeeping gene L32 and expressed as the percentage of WT levels. (B) Time course of expression of COLL I, OCN, OSX, and OPN mRNA as assessed by real-time PCR in bone marrow cultures of WT (empty symbols) and mutant (black symbols) mice, grown in osteogenic conditions. Values were normalized to time-matched levels of the housekeeping gene L32. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 versus matched WT.
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: 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.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