Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis

Malaval, Luc; Wade‐Gueye, Ndéye Marième; Boudiffa, Maya; Jia, Fu; Zirngibl, Ralph A; Chen, Frieda; Laroche, Norbert; Roux, Jean-Paul; Burt‐Pichat, Brigitte; Duboeuf, F.; Boivin, Georges; Jurdic, Pierre; Lafage‐Proust, Marie‐Hélène; Amédée, Joëlle; Vico, Laurence; Rossant, Janet; Aubin, Jane E.

doi:10.1083/jcb1814oia14

Cited by 77 publications

(142 citation statements)

References 23 publications

(26 reference statements)

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…αvβ3 integrin interacts with several bone matrix proteins, including bone sialoprotein (BSP), which is expressed at especially high levels in the primary spongiosa. Both loss-and gain-of-function mouse genetic experiments strongly support a role for Bsp in bone resorption (18,19). Expression of Bsp and several other ECM components was markedly reduced in Osx postnatal -null bones.…”

Section: Discussionmentioning

confidence: 79%

Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice

Zhou¹,

Zhang²,

Feng

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

279

255

View full text Add to dashboard Cite

The transcription factor Osterix (Osx) is required for osteoblast differentiation and bone formation during embryonic development, but it is not known whether Osx has an essential function in postnatal bone growth and in bone homeostasis. Conditional deletion of Osx at several time points postnatally revealed that Osx was essential for osteoblast differentiation and new bone formation in growing and adult bones. Additionally, inactivation of Osx in bones severely disrupted the maturation, morphology, and function of osteocytes. These findings identify Osx as having an essential role in the cell-specific genetic program of osteocytes. Interestingly, Osx inactivation also led to the massive accumulation of unresorbed calcified cartilage in a large area below the growth plate of endochondral bones. This specific area was also marked by an unanticipated almost complete lack of bone marrow cells and a marked decrease in the density and size of osteoclasts. This diminished density of osteoclasts could contribute to the lack of resorption of mineralized cartilage. In addition, we speculate that the abnormally accumulated, mainly naked cartilage represents an unfavorable substrate for osteoclasts. Our study identifies Osx as an essential multifunctional player in postnatal bone growth and homeostasis.osteoblast differentiation | skeletal homeostasis | transcription factor | osteocyte | cartilage resorption T he identification of master transcription factors essential for osteoblast differentiation and bone formation during embryonic development has greatly advanced our knowledge of bone biology. However, the transcriptional control of postnatal bone formation and homeostasis remain poorly understood. Normal skeletal growth and homeostasis depends on the coordinated activities of three types of bone cells: osteoblasts, osteoclasts, and osteocytes. Factors secreted by the mesenchyme-derived osteoblasts also control the differentiation and activity of the boneresorbing osteoclasts derived from hematopoietic stem cells. Conversely, bone resorption by osteoclasts releases factors important for bone formation. Osteocytes, which make up over 90-95% of all bone cells in adult animals, are derived from mature osteoblasts and are embedded inside the bone matrix. It has been suggested that osteocytes are mediators of mechanical and hormonal stimulations to control the activity of both osteoblasts and osteoclasts (1). Osteocytes are regulators of mineralization and mineral homeostasis (2, 3), and by controlling Sost expression also act as modulators of Wnt signaling (4).Three transcription factors [β-catenin, Runx2, and Osterix (Osx)] are required for osteoblast differentiation and bone formation during embryonic development (5-9). Osx, which acts downstream of Runx2, is a zinc-finger-containing transcription factor essential for embryonic osteoblast differentiation and bone formation (8). During development, Osx is specifically expressed in osteoblast lineage cells and, at lower levels, in prehypertrophic chondrocytes, but not in ...

show abstract

Section: Discussionmentioning

confidence: 79%

Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice

Zhou¹,

Zhang²,

Feng

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

279

255

View full text Add to dashboard Cite

show abstract

“…(6) Notably, we showed previously that fewer POCs and OCs form in cultures of BSP À/À spleen or bone marrow cells. (11) While these results clearly indicate a role for BSP in OC formation and activity, the mechanisms underlying these effects remain unclear.…”

Section: Introductionmentioning

confidence: 91%

“…(11) . Briefly, exons II-III of the mouse Bsp gene were replaced by a PGKneo cassette that created a null allele in mouse R1embryonic stem cells kindly provided by Dr. Andras Nägy.…”

Section: Generation Of Spleen-derived Osteoclastsmentioning

confidence: 99%

“…(10) Recently, we showed that adult BSP knockout mice (BSP À/À ) display a higher trabecular bone mass despite a reduced BFR and lower osteoclast surfaces and number, suggesting a dominant role of impaired bone resorption in the bone phenotype observed. (11) Raynal and colleagues (12) showed that addition of exogenous BSP promotes bone resorption when mature osteoclasts are seeded onto dentine slices, most likely through a BSP/a V b 3 integrin interaction. However, when exogenous BSP was added to cocultures of osteoblasts and spleen cells, the number of OCs generated was dose-dependently decreased.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bone sialoprotein deficiency impairs osteoclastogenesis and mineral resorption in vitro

Boudiffa

Wade‐Gueye

Guignandon

et al. 2010

Journal of Bone and Mineral Research

Self Cite

View full text Add to dashboard Cite

Bone sialoprotein (BSP) and osteopontin (OPN) migration genes (aV integrin chain and OPN) and increased expression of resorptive enzymes (TRACP and cathepsin K). The migration of preosteoclasts and mature osteoclasts is impaired in the absence of BSP, but resorption pit assays on dentine slices show no significant difference in pit numbers between BSP þ/þ and BSP À/À osteoclasts. However, resorption of mineral-coated slides by BSP À/À osteoclasts is markedly impaired but is fully restored by coating the mineral substrate with hrBSP and partly restored by hrOPN coating. In conclusion, lack of BSP affects both osteoclast formation and activity, which is in accordance with in vivo findings. Our results also suggest at least some functional redundancy between BSP and OPN that remains to be clarified. ß

show abstract

“…Immunogold labeling has shown that both BSP and OPN appear at mineralization foci (Figure 10 A) and thereafter pack in the spaces between collagen fibrils (Figure 10 B). Although BSP has been reported to accumulate and colocalize with bone acidic glycoprotein-75 at sites of mineral nucleation Midura et al 2004), a recent report revealed only slight mineral deficit in BSP knockout mice (Malaval et al 2008). The presence of lectin cytochemistry and immunolabeling for BSP and OPN have further revealed that locally, within a same bone tissue there are areas that can be either poor or enriched in NCPs (Nanci 1999).…”

Section: Distribution Of Noncollagenous Matrix Proteins In Bonementioning

confidence: 99%

Immunocytochemistry of matrix proteins in calcified tissues: functional biochemistry on section

Nanci¹,

Wazen²,

Nishio³

et al. 2009

Eur J Histochem

View full text Add to dashboard Cite

The organic matrix of calcified tissues comprises collagenous and/or noncollagenous matrix proteins (NCPs). Identification and precise mapping of these matrix components is essential for determining their function, formulating coherent hypotheses on their mechanism(s) of action, and developing novel therapeutic approaches based on biologics. Fibrillar collagen can be readily identified by its conspicuous structure, however, NCPs, in general, do not individually exhibit characteristic structural features that permit to identify them and morphologically determine their localization. To address this limitation, we have used immunocytochemistry, a form of "biochemistry on section", to correlate composition with structure. For cytochemical characterizations, including immunolabeling, our laboratory has opted for colloidal gold labelings and pioneered their application to calcified tissues because they yield high spatial resolution and are quantitative. Over the years, this approach has been applied to identify and map various NCPs in bone and teeth and, in this review of our work, we will emphasize some selected studies that highlight it application to also achieve functional information.

show abstract

Bone sialoprotein plays a functional role in bone formation and osteoclastogenesis

Cited by 77 publications

References 23 publications

Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice

Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice

Bone sialoprotein deficiency impairs osteoclastogenesis and mineral resorption in vitro

Immunocytochemistry of matrix proteins in calcified tissues: functional biochemistry on section

Contact Info

Product

Resources

About