RESEARCH
The Roles of Dentin Sialophosphoprotein in Dentinogenesis Imperfecta and Dentin Mineralization
Dentin sialophosphoprotein (DSPP) is the most abundant noncollagenous protein in the dentin matrix. It is cleaved into the N-terminal dentin sialoprotein (DSP) and the C-terminal dentin phosphoprotein (DPP). Non-syndromic Dentinogenesis Imperfecta (DGI) in humans is exclusively caused by two types of DSPP mutations. The 5’ mutations affect the secretion of the protein, wheseas the 3’ mutations that change the highly repetitive acidic DPP into hydrophobic mutant proteins. We have partially differentiated the pathological mechanisms associated with the 5’ and 3’ DSPP mutations. We have also used transgenic knockout mice to study the roles of DSP and DPP in dentin mineralization. We will further investigate the roles of DSPP in DGI and dentin mineralization by defining the relationship among the posttranslational modifications, secretion and localization of DSPP, the physiology and pathology of odontoblasts, and the ultrastructure and mineralization of dentin.
Ameloblast and Odontoblast Differentiation
Dental epithelium and mesenchyme are the two primary components in developing teeth. In both components, stem cells self-renew, proliferate, and differentiate into cells that form dental mineralized tissues, including ameloblasts and odontoblasts. How these stem cells proliferate and commit to ameloblast and odontoblast lineages remains elusive. We integrate information from bioinformatic datasets and molecular profiles in developing teeth to elucidate the differentiation trajectories of ameloblasts and odontoblasts.
Enamel Mineralization Front
Unlike dentin mineralization that occurs in a collagenous matrix, enamel mineralization is tightly associated with the distal plasma membrane of ameloblasts. Dental enamel mineral ribbons are initiated between mineralized dentin and the distal membrane of ameloblasts. They are then elongated during the secretory stage and thickened during the maturation stage. Apart from the major enamel matrix proteins, there are other molecules at the enamel mineralization front that are essential for the initiation, attachment, and elongation of enamel mineral ribbons during the secretory stage. Some of these molecules are associated with the classical basement membrane, even though the basement membrane structure is not present at the secretory stage enamel mineralization front. We use morphological, molecular, and ultrastructural approaches to study these proteins using transgenic mouse models.
