DMP1 Processing is Essential to Dentin and Jaw Formation.

Dentin matrix protein 1 (DMP1), an acidic protein that is essential to the mineralization of bone and dentin, exists as proteolytically processed fragments in the mineralized tissues. In this study, we characterized the tooth and jaw phenotypes in transgenic mice containing no wild-type DMP1, but expressing a mutant DMP1 in which Asp213, a residue at one cleavage site, was replaced by Ala213 (named “Dmp1-KO/D213A-Tg” mice). The teeth and mandible of Dmp1-KO/D213A-Tg mice were compared with those of wild-type, Dmp1-knockout (Dmp1-KO), and Dmp1 -KO mice expressing the normal Dmp1 transgene. The results showed that D213A-DMP1 was not cleaved in dentin, and the expression of D213A-DMP1 failed to rescue the defects in the dentin, cementum, and alveolar bones in the Dmp1-KO mice. These findings indicate that the proteolytic processing of DMP1 is essential to the formation and mineralization of dentin, cementum, and jaw bones. [ABSTRACT FROM PUBLISHER]