Recombinant Human DMP-1 Protein, CF

Dentin matrix protein 1 (DMP-1) is a member of the SIBLING family that also includes bone sialoprotein, dentin sialophosphoprotein, MEPE, and osteopontin. These highly phosphorylated integrin-binding proteins are rich in acidic amino acids and function in the formation of calcified bone and tooth matrix (1, 2). The phosphate content, spacing of acidic residues, and calcium-dependent dimerization of DMP-1 contribute to its ability to sequester calcium phosphate clusters and promote hydroxyapatite (HA) crystal formation (3 - 5). Rodent DMP-1 is cleaved by BMP-1 family proteases at a single site which is conserved in human, generating a 37 kDa N-terminal and a 57 kDa C-terminal fragment (6). The N-terminal fragment in rat carries chondroitin sulfate (7). The C-terminal fragment alone can nucleate HA crystals, while crystal growth into a needle-like morphology is inhibited by the N-terminal fragment (3, 4). Crystal maturation is dependent on the presence of type I collagen (4). DMP-1 is required for odontoblast differentiation as well as dentin formation (8). Nonphosphorylated DMP-1 is targeted to the nucleus, where it activates the transcription of odontoblast and osteoblast specific genes (9, 10). Early in osteoblast maturation, nuclear DMP-1 is extensively phosphorylated by casein kinase II, triggering its secretion (9). DMP-1 mutations in humans are associated with hypophosphatemia and FGF23 overexpression (11, 12). DMP-1 induces the activation of proMMP-9 and displaces mature MMP-9 from TIMP1 (13). DMP-1 tethering of MMP-9 to the cell surface via CD44 and integrins alpha v beta 3 and alpha v beta 5 promotes tumor cell invasiveness in vitro (14). Full length DMP-1 circulates in human serum in a tight complex with complement factor H (13, 14). When first bound to CD44 or integrin alpha v beta 3, DMP-1 can anchor factor H to the cell surface and protect the cell from complement-mediated lysis (15). Mature human DMP-1 shares 61% - 67% amino acid sequence identity with bovine, mouse, and rat DMP-1.