Characterization of Porcine Bone Sialoprotein: Primary Structure and Cellular Expression

Shapiro, Howard S.; Chen, Jinkun; Wrana, Jeffrey L.; Zhang, Qi; Blum, Max; Sodek, Jaro

doi:10.1016/s0934-8832(11)80109-5

Cited by 78 publications

(45 citation statements)

References 30 publications

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“…4 These principles were established using several biologically active peptides derived from bone sialoprotein (BSP), a protein originally isolated from fetal bone, which is a highly conserved glycosylated acidic protein. [5][6][7] BSP was originally identified as a possible source of osteogenic peptides, because it is the major noncollagenous protein in osseous tissue and is localized primarily around mature osteoblasts in newly formed bone. 8 Previously, a rat BSP derived RGD-containing peptide (Ac-CGGNGEPRGDTYRAY-NH 2 ) [bsp-RGD (15)] was immobilized on quartz and TiO 2 thin films, and was observed to enhance initial cell attachment and spreading and long-term cellular events (mineralized matrix formation) in a density dependent manner.…”

Section: Introductionmentioning

confidence: 99%

In vitro characterization of peptide-modified p(AAm-co-EG/AAc) IPN-coated titanium implants

et al. 2006

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Interpenetrating polymer networks (IPNs) of poly(acrylamide-co-ethylene glycol/ acrylic acid) [p(AAm-co-EG/AAc)] functionalized with an -Arg-Gly-Asp-containing peptide derived from rat bone sialoprotein [bsp-RGD(15)] were grafted to titanium implants in an effort to modulate osteoblast behavior in vitro. Surface characterization data were consistent with the presence of an IPN, and ligand density measurements established that the range of peptide density on the modified implants spanned three orders of magnitude (0.01-20 pmol/cm 2 ). In vitro biological characterization of the modified implants employing the primary rat calvarial osteoblast (RCO) model resulted in the identification of a critical ligand density (0.01 < G crit < 0.1 pmol/cm 2 ) for maximal support of the osteoblast phenotype. After 14 and 21 days, mineralization was greater on the 0.1 and 10 pmol/cm 2 bsp-RGD(15) modified implants compared to the base titanium and other control surfaces. The observed effects were attributed to specific interactions with bsp-RGD(15) and support the concept that peptide-modified implants can enhance the kinetics of differentiation of the cells they contact. These results suggest that in vivo biological performance evaluation of these biomimetic implant surfaces is merited. ß

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Section: Introductionmentioning

confidence: 99%

In vitro characterization of peptide-modified p(AAm-co-EG/AAc) IPN-coated titanium implants

et al. 2006

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“…Based on the primary sequence BSP was believed initially to maintain an open, extended structure with regions that had the ability to form both ␣-helical and ␤-sheet structure (20). However, nuclear magnetic resonance (NMR) studies have indicated a loose open structure for a 55-residue peptide containing the RGD cell attachment sequence (21), whereas more recent studies on full-length, fully modified BSP by one-dimensional NMR also showed an unstructured, flexible conformation in solution, with no ␣-helical and ␤-sheet structure present (22).…”

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Delineation of the Hydroxyapatite-nucleating Domains of Bone Sialoprotein

Tye

Rattray

Warner

et al. 2003

Journal of Biological Chemistry

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Bone sialoprotein (BSP) is a highly modified, anionic phosphoprotein that is expressed almost exclusively in mineralizing connective tissues and has been shown to be a potent nucleator of hydroxyapatite (HA). Two polyglutamic acid (poly[E]) regions, predicted to be in an ␣-helical conformation and located in the amino-terminal half of the molecule, are believed to be responsible for this activity. Using a prokaryotic expression system, full-length rat BSP was expressed and tested for HA nucleating activity in a steady-state agarose gel system. The unmodified protein is less potent than native bone BSP, indicating a role for the post-translational modifications in HA nucleation. domains, were expressed and tested for nucleating activity. Whereas the peptide encompassing the second poly[E] domain was capable of nucleating HA, the first domain peptide showed no activity. The conformation of the wild-type and mutated proteins and peptides were studied by circular dichroism and small angle x-ray scattering, and no secondary structure was evident. These results demonstrate that a sequence of at least eight contiguous glutamic acid residues is required for the nucleation of HA by BSP and that this nucleating "site" is not ␣-helical in conformation.Mineralization of the extracellular matrix in bone, dentin, and cementum is a complex, poorly understood process that is believed to involve both hydroxyapatite-nucleating and -modulating noncollagenous proteins. In bone, it has been postulated that type I collagen acts as a structural matrix, whereas HA nucleation is mediated by an anionic phosphoprotein (1-3). Of the noncollagenous proteins, bone sialoprotein (BSP) 1 is the most likely candidate. The highly anionic nature of BSP and its spatio-temporal pattern of expression have led investigators to propose a role of this protein in the mineralization of bone (1-4).Mammalian BSPs contain an average of 327 amino acids, which includes a 16-residue signal sequence. The protein has a molecular mass of ϳ33-34 kDa. However, post-translational modifications, including both N-and O-linked glycosylation, tyrosine sulfation, and serine and threonine phosphorylation, constitute 50% of the total mature protein weight of ϳ75 kDa. Analysis of the mammalian BSP cDNAs reveals a 45% level of sequence identity, plus an additional 10 -23% in conservative replacements. However, identity of up to 90% is observed in and around two polyglutamic acid sequences (poly[E]); an ArgGly-Asp (RGD) cell-binding motif; sites of phosphorylation, sulfation, and glycosylation; and sequences near the amino and carboxyl termini, which are rich in tyrosine residues (5).Normally BSP expression is limited almost exclusively to mineralized connective tissues, and its expression is localized to areas of bone formation. By in situ hybridization, it has been shown that BSP expression occurs in osteoblasts actively engaged in bone formation and is found at low or undetectable levels in other regions of mineralized tissue (6 -11). Transfection of BSP into nonmineralizin...

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“…BSP is a phosphorylated 70-80 kDa glycoprotein that accounts for 5-10% of the non-collagenous bone matrix (Fisher et al, 1983;Heinegard and Oldberg, 1989). The protein is a major synthetic product of active osteo-and odontoblasts and contains an ArgGly-Asp (RGD) sequence (Chen et al, 1991;Fujisawa et al, 1993;Shapiro et al, 1993). This sequence is recognized by various integrin receptors including the αrβ 3 vitronectin receptor (CD51/CD61) (Oldberg et al, 1988;Ross et al, 1993), which is expressed by osteoclasts (Ross et al, 1993).…”

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confidence: 99%

“…Thus, in the course of normal bone remodelling, BSP is likely to be involved in the adhesion of bone resorbing cells to the extracellular bone matrix (Helfrich et al, 1992). Although preferentially detected in the cells of mineralized tissues (Fisher et al, 1983;Chen et al, 1991;Shapiro et al, 1993), BSP has been found to be ectopically expressed in the cytoplasma and on the surface of myeloma cells (Bellahcène et al, 1996b) and of tumour cells of other malignancies (Bellahcène et al, 1994). In Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma studies of breast cancer patients, BSP was found to be associated with the appearance of bone metastases, suggesting that BSP may be involved in the molecular mechanisms responsible for cancer cell osteotropism (Bellahcène et al, 1996a;Diel et al, 1999).…”

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confidence: 99%

Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma

Pecherstorfer

Horn

et al. 2001

Br J Cancer

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SummaryTo test the potential of immunoreactive BSP, a non-collagenous bone matrix component, as a clinical guide in patients with plasma cell dyscrasias, serum BSP concentrations were measured in 62 patients with newly diagnosed multiple myeloma (MM) followed over a period of 4 years, in 46 patients with monoclonal gammopathy of undetermined significance (MGUS), in 71 patients with untreated benign vertebral osteoporosis (OPO), and in 139 healthy adults. Results were compared with clinical and laboratory data, including serum osteocalcin (OC), and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) as markers of bone turnover. In MM, serum BSP, and urinary PYD and DPD were higher than in healthy controls and in MGUS or OPO (P < 0.001). BSP levels correlated with the bone marrow plasma cell content (r = 0.40, P < 0.001), and serum β 2 -microglobulin (r = 0.31, P < 0.01). The differentiation of MM from healthy controls and from MGUS or OPO was highest for BSP. After chemotherapy, BSP reflected the response to treatment and correlated with the change in monoclonal protein (r = 0.55, P < 0.001). MM patients with normal baseline BSP levels survived longer than patients with initially elevated BSP values (P < 0.001, logrank test). Only serum monoclonal protein and BSP were independent predictors of survival. We conclude that in MM, BSP levels are associated with skeletal involvement and tumour cell burden. The quantification of serum BSP may be a non-invasive method for the diagnosis and follow-up, and may improve the prognostic value of conventional staging in MM.

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Characterization of Porcine Bone Sialoprotein: Primary Structure and Cellular Expression

Cited by 78 publications

References 30 publications

In vitro characterization of peptide-modified p(AAm-co-EG/AAc) IPN-coated titanium implants

In vitro characterization of peptide-modified p(AAm-co-EG/AAc) IPN-coated titanium implants

Delineation of the Hydroxyapatite-nucleating Domains of Bone Sialoprotein

Serum bone sialoprotein as a marker of tumour burden and neoplastic bone involvement and as a prognostic factor in multiple myeloma

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