Does Enhanced Dentin Sialophosphoprotein (DSPP) Expression Affect Runx2 Expression in Tooth Development?

Epithelial-mesenchymal interactions lead to Runx2 expression in mesenchyme in bud, cap and early bell stages. At late bell stage, DSPP expression appears in odontoblasts and dental pulp but no more Runx2 expression. Runx2 is required for proper tooth development from bud, cap to early and bell stages. Runx2 Knockout (KO) mice showed defective enamel organ lacked overt odontoblasts and ameloblast differentiation. It is interesting that while Runx2 expresses in bud, cap and early bell stages, no DSPP expression is detected in these stages. When DSPP expresses actively in mesenchyme at late bell stage, no Runx2 expression is detected in mesenchyme. This reciprocal expression of Runx2 and DSPP (i.e., Runx2 down and DSPP up in late Bell stage) posted the possibility that DSPP expression in late bell stage of Wild Type (WT) mice might down-regulate Runx2 expression. DSPP protein is cleaved into Dentin Sialoprotin (DSP) and Phosphophoryn (PP). Recently, we reported that DSP/PP can reduce cell proliferation and promote cell differentiation and DSP/PP can function as signal molecules during tooth development. Objective: To better understand the mechanism for the exclusive expression patterns of Runx2 and DSPP expression during tooth development, we investigated (1) whether recombinant DSP/PP (recDSP/PP) can affect Runx2 expression in human dental pulp stem cells (hDPSCs) and (2) whether the absence of DSPP in DSPP KO changed Runx2 expression in molars and incisors. Methods: recDSP/PP was used to test its effect on Runx2 expression in hDPSCs. Using immunohistochemical analyses and RealTime PCR analyses, we examined Runx2 expression in WT and DSPP KO mouse teeth. Results: We found that the presence of recDSP/PP does not affect Runx2 expression in-vitro. Absence of DSPP expression in newborn DSPP-KO molar up regulates Runx2 expression in-vivo. Conclusion: Appropriate temporal and spatial expression of Runx2 and DSPP are required for normal tooth development.