Multifunctional Role of Dentin Matrix Protein 1 in Vertebrate Mineralization

DMP1encodes a serine-rich acidic protein and is a member of Small Integrin- Binding Ligand, N-linked, Glycoprotein family (SIBLING) which mineralizes tissues such as bones and teeth by binding strongly to hydroxyapatite. Dual functions of the DMP1 protein have been reported based on the in vitro studies. The nonphosphorylated cytoplasmic DMP1 protein translocates to the cell nucleus and initially acts as a transcriptional factor to enhance gene transcription of the osteoblast-specific genes such as alkaline phosphatase and osteocalcin and then moves out to the extracellular matrix during the osteoblast to osteocyte transition phase to promote mineralization and phosphate homeostasis. Loss of function mutations in the human DMP1 gene have been shown to cause autosomal recessive hypophosphatemic rickets in different ethnic groups. These variant mutations in DMP1 include deletions in exon 6, nucleotide substitution in the splice acceptor sequence of intron 2, and missense mutations in exons 2 or exon 3 that introduce the premature termination codon. The DMP1-null mouse also exhibits hypophosphatemic rickets which indicates the important role of the DMP1 gene in the development of normal bone formation. Most of the functional domains identified thus far are encoded by the sixth and last exon of DMP1.

Keywords: Dentin matrix protein 1, SIBLINGs, transcriptional factor, hypophosphatemic rickets, biomineralization, hydroxyapatite, calcium, signaling, collagen, bone, dentin, noncollagenous proteins, scaffold, extracellular matrix, phosphoproteins, GRP-78, kinase, MAP kinase.