Priyam Jani1, Hua Zhang1, M Douglas Benson2, Chunlin Qin3. 1. Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA. 2. Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA. Electronic address: mdbenson@tamu.edu. 3. Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University College of Dentistry, 3302 Gaston Ave, Dallas, TX, 75246, USA. Electronic address: chunlinqin@tamu.edu.
Abstract
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 Tgfβ 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 Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.
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 Tgfβ 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 Tgfβ ligands, in addition to BMPs, play a crucial role in post-developmental dentinogenesis.