Role of the small integrin-binding ligand N-linked glycoprotein (SIBLING), bone sialoprotein (BSP) in bone development and remodeling.

摘要

Between cell and mineral-the SIBLINGS The "small, integrin binding ligand, TV-linked glycoprotein" family (SIBLINGS, [1]) group osteopontin (OPN), bone sialoprotein (BSP), dentin sialophosphoprotein (DSPP), dentin matrix protein-1 (DMP-1) and matrix extracellular glycophosphoprotein (MEPE). The genes for this family are aligned on a portion of human chromosome 4 (mouse chromosome 5), within a "Bone Gene Cluster" [2, 3] grouping other genes of bone interest. Molecular evolution studies [4, 5] suggest that SIBLINGS, along with enamelins and other proteins found in milk (caseins) and saliva (statherin), form a "Secretory Calcium binding Phospho- Proteins" (SCPP) family [4], sharing as a common ancestor Hevin [6], and more precisely the long N-terminal domain that distinguishes it from the related protein SPARC (secreted protein, acidic and rich in cystein)/Osteonectin [7]. The SCPP share a flexible structure, and many contain numerous acidic aminoacid residues, which favour interactions with crystals (review in [8]). The SIBLINGS, more specifically, have acidic pI (with the exception of MEPE), and display in their sequence a proline-rich stretch (basic), consensus sites for casein-kinase, an arginine-glycine-aspartic acid (RGD) sequence-binding integrin family receptors, and (apart for BSP) one or several ASARM (acidic serine-aspartate rich MEPE associated) peptides, which have a high affinity for hydroxyapatite and appear to be potent regulators of mineralization [9, 10]. The SIBLINGS also display a high degree of post-translational modification (phosphorylation, sulfatation and/or glycosylation) which varies for a given protein in time (cellular differentiation) and space (tissue), and directly affects their biological functions (review in [11]). In bone, the SIBLINGS are expressed by cells of the osteoblast lineage, DMP-1 and MEPE being mostly restricted to osteocytes. OPN and BSP at least are also expressed by hypertrophic chondrocytes and osteoclasts. SIBLINGS are also present in multiple non-mineralized tissues, especially with secretory functions (salivary glands, kidney, [12, 13]) and by cancer cells in which they favour metastatic processes, particularly targeting bone (review in [14]).