The role of bone morphogenetic proteins 2 and 4 in mouse dentinogenesis

Objective: The bone morphogenetic proteins (BMPs) play crucial roles in tooth development. However, several BMPs retain expression in the dentin of the fully patterned and differentiated tooth. We hypothesized that BMP signaling therefore plays a role in the function of the differentiated odontoblast, the job of which is to lay down and mineralize the dentin matrix. Design: We generated mice deficient in Bmp2 and 4 using a dentin matrix protein 1 (Dmpl) promoter-driven cre recombinase that was expressed in differentiated odontoblasts. Results: The first and second molars of these Bmp2 and Bmp4 double conditional knockout (DcKO) mice displayed reduced dentin and enlarged pulp chambers compared to cre-negative littermate controls. DcKO mouse dentin in first molars was characterized by small, disorganized dentinal fibers, a wider predentin layer, and reduced expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), and bone sialoprotein (BSP). DcKO mouse odontoblasts demonstrated increased type I collagen mRNA production, indicating that the loss of BMP signaling altered the rate of collagen gene expression in these cells. Bmp2 and Bmp4 single Dmpl-cre knockout mice displayed no discernable dentin phenotype. Conclusions: These data demonstrate that BMP signaling in differentiated odontoblasts is necessary for proper dentin production in mature teeth.