Site-specific function and regulation of Osterix in tooth root formation

Abstract

Congenital diseases of tooth roots, in terms of developmental abnormalities of short and thin root phenotypes, can lead to loss of teeth. A more complete understanding of the genetic molecular pathways and biological processes controlling tooth root formation is required. Recent studies have revealed that Osterix (Osx), a key mesenchymal transcriptional factor participating in both the processes of osteogenesis and odontogenesis, plays a vital role underlying the mechanisms of developmental differences between root and crown. During tooth development, Osx expression has been identified from late embryonic to postnatal stages when the tooth root develops, particularly in odontoblasts and cementoblasts to promote their differentiation and mineralization. Furthermore, the site-specific function of Osx in tooth root formation has been confirmed, because odontoblastic Osx-conditional knockout mice demonstrate primarily short and thin root phenotypes with no apparent abnormalities in the crown (Journal of Bone and Mineral Research 30, 2014 and 742, Journal of Dental Research 94, 2015 and 430). These findings suggest that Osx functions to promote odontoblast and cementoblast differentiation and root elongation only in root, but not in crown formation. Mechanistic research shows regulatory networks of Osx expression, which can be controlled through manipulating the epithelial BMP signalling, mesenchymal Runx2 expression and cellular phosphorylation levels, indicating feasible routes of promoting Osx expression postnatally (Journal of Cellular Biochemistry 114, 2013 and 975). In this regard, a promising approach might be available to regenerate the congenitally diseased root and that regenerative therapy would be the best choice for patients with developmental tooth diseases.

Keywords: Osterix; dentinogenesis; odontoblast differentiation; tooth root development.

Figure 1

Genetic and epigenetic regulations of Osx expression. The expression of Osx is positively regulated by both epithelial signals such as BMP and mesenchymal factors including Runx2, Nfic, Dlx5, etc. Therefore, these upstream molecules could become the targets to manipulate Osx expression. Osx is crucial to the differentiation of apical odontoblasts and cementoblasts and the expression of matrix proteins during tooth root development, which is supported by short and thin root dentine but normal crown phenotypes of odontoblastic Osx-cKO mice.