Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice overexpressing transforming growth factor-beta 1 in teeth

Transforming growth factor (TGF)-beta1 is expressed in developing tooth fro m the initiation stage through adulthood. Odontoblast-specific expression o f TGF-beta1 in the tooth continues throughout life; however, the precise bi ological functions of this growth factor in the odontoblasts are not clearl y understood. Herein, we describe the generation of transgenic mice that ov erexpress active TGF-beta1 predominantly in the odontoblasts, Teeth of thes e mice show a significant reduction in the tooth mineralization, defective dentin formation, and a relatively high branching of dentinal tubules, Dent in extracellular matrix components such as type I and III collagens are inc reased and deposited abnormally in the dental pulp, similar to the heredita ry human tooth disorders such as dentin dysplasia and dentinogenesis imperf ecta, Calcium, one of the crucial inorganic components of mineralization, i s also apparently increased in the transgenic mouse teeth. Most importantly , the expression of dentin sialophosphoprotein (dspp), a candidate gene imp licated in dentinogenesis imperfecta II (MIM 125420), is significantly down -regulated in the transgenic teeth. Our results provide in vivo evidence su ggesting that TGF-beta1 mediated expression of dspp is crucial for dentin m ineralization, These findings also provide for the first time a direct expe rimental evidence indicating that decreased dspp gene expression along with the other cellular changes in odontoblasts may result in human hereditary dental disorders like dentinogenesis imperfecta II (MIM 125420) and dentin dysplasia (MIM 125400 and 125420).