Bone sialoprotein

The search for a protein nucleator of hydroxyapatite crystal formation has been a focus for the isolation and characterization of the major non-collag enous proteins in bone. Of the proteins characterized to date, bone sialopr otein (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, polyglu tamic acid and arginine-glycine-aspartate (RGD) motifs with the ability to bind hydroxyapatite and cell-surface integrins, respectively, have been con served in the protein sequence. Expression of the BSP gene, which is induce d in newly formed osteoblasts, is up-regulated by hormones and cytokines th at promote bone formation and down-regulated by factors that suppress bone formation. Thus, BSP has the biophysical and chemical properties of a nucle ator, and its temporo-spatial expression coincides with de Move mineralizat ion in bone and cementum. Moreover, BSP has been associated with mineral cr ystal formation in several pathologies, including breast carcinomas. Howeve r, the ability of BSP to mediate cell attachment and to signal through the RGD motif points to alternate functions for BSP which need further investig ation. In combination, the hydroxyapatite-binding polyglutamic acid sequenc es 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.