The long term objective is to understand the role played by the extracellular matrix protein, phosphoprotein (PP) in biomineralization especially of dentin. Dentin phosphoprotein (DPP) has a great affinity for both calcium and collagen and appears to be the nucleator of mineral and controller of crystal growth in dentin. By better understanding the role of DPP it will be possible to devise preventive and/or therapies that will ameliorate tooth aplasia, tooth malformations and faulty repair in response to caries and cavity preparation. In rat and mouse DPP appears to be a cleavage product of a single transcript that is encoded for by the provisionally named dentin sialophosphoprotein gene (Ritchie and Wang, 1996, MacDougall et al., 1997). Recently the applicant in collaborations with Drs. Ritchie and Rutherford have cloned the human DSPP gene (Gu, et al. 1998 and unpublished data) and it is now possible to use in vitro expression systems and site specific mutagenesis to produce active and mutant recombinant proteins that can be used to assess the functional role of DPP in human dentin mineralization. Thus the following specific aims will test the hypothesis that DPP is the major nuclear and controller of crystal hydroxyapatite growth in dentin by: (i) Inducing and controlling hydroxyapatite crystal growth using recombinant and naturally sourced DPP's in an in vitro system. (ii) Assessing the ability of odontoblasts to significantly express transduced wild type or mutant DPP in a human tissue culture system.
