Poster Sessions

Dev-34

Shigeki Suzuki

S. Suzuki, C. Honeycutt, T. Sreenath, A. Terse, N. Haruyama, M. Goldberg, A. B. Kulkarni

Molecular Roles of Dentin Sialophosphoprotein in Tooth Development and Mineralization

Oblective: Our research is focused on understanding the molecular roles of dentin sialophosphoprotein (DSPP) in tooth development and mineralization. Tooth development is initiated by oral epithelium and mesenchyme interaction. DSPP is mainly expressed late stage of tooth development in dentin, which is the main portion of tooth and originated from mesenchyme. It is the most abundant noncollagenous extracellular matrix protein and belong to the small integrin-binding ligand N-linked glycoprotein (SIBLING) family as well as osteopontin, bone sialoprotein. It is implicated in one of the most common hereditary tooth disorder, dentinogenesi imperfecta (DGI). The mRNA is translated into a single protein, DSPP, which is cleaved into 2 peptides, dentin sialoprotein (DSP), dentin phosphoprotein(DPP). Our previous work on DSPP knockout mice (DSPP KO) confirmed the important role of DSPP in dentin mineralization. These mice develop tooth defects similar to those seen in DGI, decreased width of the dentin zone along with an increased width of the unmineralaized (predentin) zone, hypomineralization, and pulp exposure. Many previous reports using in vitro model suggested that DPP is highly phsphorelated therefore it can work as strong initiator for dentin mineralization. On the other hand, the roles of DSP were less understood. Several in vitro study suggested, rather, DSP had limited or no effect for dentin mineralization. Our objective for the current work was to delineate the precise molecular roles of DSP and DPP in dentin development and mineralization in vivo. Methods: We constructed transgenic vectors that express DSP under the control of the DSPP promoter and generated independent transgenic lines (DSPTgKO) that express DSP in odontoblasts, which is only one kind of cell to make dentin, in a DSPP-null background. Results: We have established 2 DSPTgKO transgenic mouse lines that express DSP at low and high levels. Unexpectedly, dentin width of DSP TgKO teeth is thicker than that of DSPP KO teeth. Moreover, frequency of pulp exposure in DSPTgKO is much less than DSPP KO and unmineralized zone of DSP TgKO teeth are narrower than that of DSPP KO. These phenotypes are much clear in high expression level line. These results indicated that DSP has a potent to induce dentin mineralization as well as DPP contrary to previous in vitro data. This is the first report to reveal the roles of DSP in vivo and might suggest the mechanisms of human disease DGI.