Overexpression of Sp7 in odontoblasts results in dentinogenesis imperfecta due to the inhibition of odontoblast maturation

Abstract

ObjectiveSp7 is required for cellular cementum formation and odontoblast differentiation in the root. Sp7 is expressed in preodontoblasts and is strongly expressed in odontoblasts. However, Sp7 expression was down-regulated in odontoblasts in the crown after root formation. We examined osteoblast/odontoblast-specific Sp7 transgenic mice to investigate the effects of sustained Sp7 expression in differentiated odontoblasts. MethodsTooth development was examined by immunohistochemical analyses, using antibodies against Sp7, pro-collagen type1a1, osteocalcin, dentin sialoprotein (DSP), nestin, and osteopontin. ResultsIn 1-week-old Sp7 transgenic mice, the thickness of dentin was slightly reduced, the elongation of odontoblasts was inhibited, and odontoblasts in the cusp lost polarity. At 2 weeks of age, Sp7 was strongly expressed in odontoblasts in the root, but weakly expressed in the crown of wild-type mice. It was strongly expressed in odontoblasts in the crown and root and the thinning of dentin and impairments in elongation and polarization in odontoblasts were severe in the crown of Sp7 transgenic mice. Tooth fracture and pulp exposure occurred after tooth eruption. Expression of dentin matrix proteins (DSP and osteocalcin) and nestin were reduced, whereas the osteoblast marker gene, osteopontin, was not expressed in the odontoblasts of Sp7 transgenic mice. ConclusionsThese results indicate that sustained Sp7 expression in differentiated odontoblasts inhibits odontoblast maturation and reduces the expression of dentin matrix proteins; however, it fails to induce the transdifferentiation of odontoblasts into osteoblasts, which occurs in Runx2 transgenic mice. Therefore, Sp7 expression needs to be down-regulated to an appropriate level for odontoblast maturation.