title: 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.
authors.affiliation: Medical Research Council Group in Periodontal Physiology, Faculty of Dentistry, University of Toronto, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Ganss
authors.forename: R H
authors.initials: RH
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Sodek
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D003460:Crystallization; D017886:Durapatite / Q000737:chemistry*; D005786:Gene Expression Regulation; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D012795:Sialoglycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D009363:Neoplasm Proteins; D012795:Sialoglycoproteins; D017886:Durapatite