Bone Sialoprotein

Abstract

The search for a protein nucleator of hydroxyapatite crystal formation has been a focus for the isolation and characterization of the major non-collagenous proteins in bone. Of the proteins characterized to date, bone sialoprotein (BSP) has emerged as the only bona fide candidate for nucleation. BSP is a highly glycosylated and sulphated phosphoprotein that is found almost exclusively in mineralized connective tissues. Characteristically, polyglutamic acid and arginine-glycine-aspartate (RGD) motifs with the ability to bind hydroxyapatite and cell-surface integrins, respectively, have been conserved in the protein sequence. Expression of the BSP gene, which is induced in newly formed osteoblasts, is up-regulated by hormones and cytokines that promote bone formation and down-regulated by factors that suppress bone formation. Thus, BSP has the biophysical and chemical properties of a nucleator, and its temporo-spatial expression coincides with de novo mineralization in bone and cementum. Moreover, BSP has been associated with mineral crystal formation in several pathologies, including breast carcinomas. However, the ability of BSP to mediate cell attachment and to signal through the RGD motif points to alternate functions for BSP which need further investigation. In combination, the hydroxyapatite-binding polyglutamic acid sequences and the RGD provide bi-functional entities through which BSP may mediate the targeting and attachment of normal and metastasizing cells to the bone surface.

Identification and characterization of integrin-binding sialoprotein (IBSP) genes in reptile and amphibian

“…To date, the DSPP and MEPE genes have been only in mammalian genomes (Kawasaki and Weiss, 2006;Kawasaki et al, 2007), however, IBSP, SPP1, and DMP1 have functional similarities (Fisher et al, 2001), with IBSP and SPP1 especially noted to share some structural and characteristic features (Alford and Hankenson, 2006). These three proteins have been cloned from chickens (Ganss et al, 1999;Sodek et al, 2000;Toyosawa et al, 2000), while the DMP1 gene has been cloned from a crocodile (Toyosawa et al, 1999). In this study, we attempted to identify IBSP orthologs in lower tetrapods, since it is relatively specific for calcified tissues (Ganss et al, 1999), whereas the SPP1 gene is widely expressed in soft tissues such as epithelial cells, macrophages, and lymphocytes (Sodek et al, 2000).…”

“…These three proteins have been cloned from chickens (Ganss et al, 1999;Sodek et al, 2000;Toyosawa et al, 2000), while the DMP1 gene has been cloned from a crocodile (Toyosawa et al, 1999). In this study, we attempted to identify IBSP orthologs in lower tetrapods, since it is relatively specific for calcified tissues (Ganss et al, 1999), whereas the SPP1 gene is widely expressed in soft tissues such as epithelial cells, macrophages, and lymphocytes (Sodek et al, 2000). Herein, we present our findings of IBSP-encoding cDNAs isolated from a caiman and an African clawed toad, used as reptile and amphibian subjects, respectively.…”

Osteopontin is an argentophilic protein in the bone matrix and in cells of kidney convoluted tubules

“…Although collagen account for more than 90% of the organic phase, more than 200 other proteins have been identified by biochemical analysis and their respective roles are either partially elucided or still completely unknown at that time. Several proteins are synthetized by osteoblasts and embedded in the matrix at the time of osteoid deposition (e.g., alkaline phosphatase, bone sialoprotein -BSP, osteocalcine, bone morphogenetic proteins…) [1,2].…”

Characterization of a rat model with site‐specific bone metastasis induced by MDA‐MB‐231 breast cancer cells and its application to the effects of an antibody against bone sialoprotein

“…5 This glycoprotein is relatively specific for the tissues of the skeleton and is known to have a high binding affinity for calcium and hydroxyapatite. 5,6 To further investigate the function of BSP in the course of bone metastasis formation, we set up an animal model that would allow following processes such as tumor cell extravasation, adhesion to the target tissue and formation of osteolytic lesions.For this complex scenario, animal models are indispensable tools to investigate the pathogenesis of bone metastasis in vivo and to examine the effects of a therapeutic intervention. For inducing breast cancer bone metastasis in rodents, most experimental models require the injection of human cancer xenografts into immunodeficient mice.…”

“…5 This glycoprotein is relatively specific for the tissues of the skeleton and is known to have a high binding affinity for calcium and hydroxyapatite. 5,6 To further investigate the function of BSP in the course of bone metastasis formation, we set up an animal model that would allow following processes such as tumor cell extravasation, adhesion to the target tissue and formation of osteolytic lesions.…”