Competing roles of TGFbeta and Nma/BAMBI in odontoblasts.

Nma/BAMBI is a novel pseudoreceptor with homology to a TGFbeta type I receptor that lacks a serine/threonine kinase domain. Nma/BAMBI functions as a dominant-negative protein that regulates reciprocal epithelial-mesenchymal interactions during organogenesis. Therefore, we hypothesized that Nma/BAMBI regulates TGFbeta signaling and downstream gene expression during dentinogenesis. To test this hypothesis, we examined the downstream gene expression profiles of major dentin extracellular matrix proteins in response to Nma/BAMBI, and we examined the roles of Nma/BAMBI and TGFbeta-1 during dentinogenesis. Overexpression of Nma/BAMBI in the mouse odontoblast-like cell line MD10-A2 down-regulated expression of DSPP by 66% and up-regulated expression of DMP1 four-fold. TGFbeta treatment reversed Nma/BAMBI's negative effect on DSPP expression. Furthermore, we demonstrated that TGFbeta negatively regulates Nma/BAMBI's expression levels in MD10-A2 odontoblast-like cells. Analysis of these data, together, indicates that TGFbeta and Nma/BAMBI are inversely regulated and that the sequence of expression determines the net effect on downstream gene expression.