| First Author | Jani P | Year | 2020 |
| Journal | J Oral Biosci | Volume | 62 |
| Issue | 1 | Pages | 72-79 |
| PubMed ID | 31862386 | Mgi Jnum | J:293548 |
| Mgi Id | MGI:6453466 | Doi | 10.1016/j.job.2019.11.001 |
| Citation | Jani P, et al. (2020) Noggin inhibition of mouse dentinogenesis. J Oral Biosci 62(1):72-79 |
| abstractText | OBJECTIVES: The Bone Morphogenetic Proteins (BMPs) direct tooth development and still express in the adult tooth. We hypothesized that inhibition of BMP function would therefore disrupt dentinogenesis by differentiated odontoblasts. METHODS: We generated mice overexpressing the BMP-inhibitory protein Noggin in differentiated odontoblasts and osteocytes under control of a Dmp1 promoter-driven cre transgene. We compared the dentin phenotype in these mice with that in WT littermates and in mice with a Smad4 odontoblast/osteocyte knockout mediated by the same cre and therefore lacking all BMP and Tgfbeta signaling in the same tissues. RESULTS: Three-month-old first molars from both Noggin-expressing and Smad4-deleted mice showed decreased dentin volume with enlarged pulp cavities, and both displayed less organized and mineralized dentinal tubules compared to WT. The Smad4-ablated phenotype was more severe. While dentin sialophosphoprotein (DSPP) and bone sialoprotein (BSP) were decreased in the dentin of both lines, dentin matrix protein 1 (DMP1) was sharply increased in Noggin-expressing teeth. CONCLUSIONS: The phenotypes we observed in Noggin-overexpressing and Smad4-conditional knockout teeth resemble the phenotype of Dentinogenesis Imperfecta (DGI) type III. Our results show that BMPs regulate post-natal dentinogenesis and that BMP-inhibitory proteins like Noggin play a role in that regulation. The increased severity of the Smad4 phenotype indicates that Tgfbeta ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis. |
