Dentin phosphoprotein in dentin development: implications in dentinogenesis imperfecta.

Dentin phosphoprotein (DPP, phosphophoryn) is the major non-collagenous protein component of the dentin extracellular matrix. This highly acidic phosphorylated protein is solely expressed by ectomesenchymal-derived odontoblast cells of the tooth organ. Previous biochemical studies have suggested the absence of this protein associated with the human genetic disease dentinogenesis imperfecta (DGI) Types I and II. However, due to the normal degradation of human DPP during dentin maturation, it has not been possible to establish if these reported differences were due to changes in DPP expression or secondary degradation rates in DGI affected versus normal teeth. Recently, we have taken both a molecular and biochemical approach to address this problem. Molecular studies have utilized genetic linkage studies performed on several multi-generation informative DGI kindreds. These studies have determined linkage between DGI Types II and III and two markers localized to the long arm of human chromosome 4 in the region 4q11-4q21. The strategy used in our study was to map the DPP gene locus to the long arm of human chromosome 4, in the same region as DGI, using a DPP oligonucleotide probe and somatic hybrid cell lines. The results indicate DPP is not localized to any region of human chromosome 4. Our data indicates that a mutation within the DPP gene locus is not associated with DGI Types II or III. This data is supported by the identification of human DPP (95 kDa) within the dentin extracellular matrix of molars isolated from an affected DGI type II patient using a mouse anti-DPP antibody. However, this does not exclude the possibility that enzymes associated with DPP post-translational modifications (ie. phosphorylation or degradation) might be responsible for this genetic disease.