| Dentin sialophosphoprotein (DSPP) is a large protein that undergoes proteolytic processing to form the NH2-terminal fragment [dentin sialoprotein (DSP) and its proteoglycan form (DSP-PG)] and COOH terminal fragment [dentin phosphoprotein (DPP)]. The importance of DSPP in dentinogenesis is supported by experiments showing association of mutations in the DSPP gene with human dentinogenesis imperfecta. While studies have demonstrated the critical role of DSPP in dentin formation, mechanisms by which DSPP functions in biomineralization remain largely unclear. This dissertation is a comprehensive effort to outline the function of this protein and its cleaved fragments. Both DSP/DSP-PG and DPP are abundant in the dentin extracellular matrix (ECM) whereas the protein representing the entire sequence, DSPP is scarcely present, which leads to the belief that the processed fragments may be the functional forms of DSPP. To prove this, the first part of this study analyzed the importance of the proteolytic processing of DSPP by blocking the proteolytic fragmentation. Several in vitro mineralization studies have indicated that DPP is an important initiator and modulator for the formation and growth of hydroxyapatite crystals. However, the information regarding the roles of DSP and DSP-PG are still lacking. In the second part of this study we analyzed the role of the NH2-terminal fragment of DSPP (DSP/DSP-PG) in dentinogenesis. Our investigation from these two studies showed that the proteolytic processing of DSPP is indeed an activation event, which releases the functional fragments that have distinct roles in dentinogenesis. We also discovered that the role of the NH2-terminal fragment of DSPP (DSP/DSP-PG) is to prevent the predentin from being mineralized too rapidly and to serve as an antagonist of DPP in dentinogenesis. The third and fourth part of this study emphasized the novel expression of DSPP in several non-mineralized tissues and its function in maintaining the integrity of the periodontal tissues respectively. Finally, in the fifth part of the study, we explored the interaction between the two similar non-collagenous proteins (NCPs); dentin matrix protein 1 (DMP1) and DSPP. In conclusion, the data from these five studies are vital to delineate the different roles of DSPP in biomineralization. |
