Role of NH2-terminal Fragment of Dentin Sialophosphoprotein (DSPP) in Dentinogenesis

Objectives: DSPP is a large precursor protein that is proteolytically processed to form the NH₂-terminal fragment and COOH-terminal fragment. The NH₂-terminal fragment of DSPP exists in two forms: dentin sialoprotein (DSP) and its proteoglycan form termed DSP-PG, while the COOH-terminal fragment exists in only one form known as dentin phosphoprotein (DPP). While studies have indicated that DPP is a strong initiator and regulator of hydroxylapatite crystal formation and growth, the roles of the NH₂-terminal fragment of DSPP (i.e., DSP and DSP-PG) in dentinogenesis are still unclear.  The abundance of DSP, DSP-PG and DPP, along with the scarcity of DSPP in the extracellular matrix (ECM) of dentin suggests that the proteolytic processing of DSPP may be an activation step, which releases the functional fragments that have different roles in dentinogenesis. The primary objective of this study was to examine the function of the NH₂-terminal fragment of DSPP in dentinogenesis. 

Methods: Transgenic mouse lines expressing the NH₂-terminal fragment of DSPP driven by a type I collagen promoter (Col 1a1) were generated. The transgenic mice expressing the NH₂-terminal fragment of DSPP were crossbred with Dspp null mice to obtain mice that express the transgene but lack the endogenous Dspp (designated as “DSP/Dspp null”). The teeth and jaws from these mice were characterized using biochemical, radiological and morphological approaches.

Results: The enamel and dentin of the DSP/Dspp null mice appeared to be thinner than Dspp null mice with larger pulp space. Scanning electon microscopy revealed defective osteocytes with reduced canaliculi of the DSP/Dspp null mice. 

Conclusions: We conclude that the NH₂-terminal fragment of DSPP inhibits the mineralization of dentin serving as an antagonist against DPP thus preventing predentin from being mineralized too rapidly.