Gadd45g regulates dental epithelial cell proliferation through p38 MAPK-mediated p21 expression.

Ectodermal organs, such as teeth, hair follicles, and mammary glands, arise from their respective germs through epithelial-mesenchymal interactions during organogenesis. Growth arrest and DNA damage-inducible gene gamma (Gadd45g) have been shown to play important roles in various biological processes, such as stress responses, cell differentiation, and tumor suppression, through the regulation of cell proliferation and gene expression. We found that Gadd45g was expressed in enamel knots, which orchestrate tooth germ development as epithelial signaling centers.

Dpysl4 is involved in tooth germ morphogenesis through growth regulation, polarization and differentiation of dental epithelial cells.

Dihydropyrimidinase-related protein 4 (Dpysl4) is a known regulator of hippocampal neuron development. Here, we report that Dpysl4 is involved in growth regulation, polarization and differentiation of dental epithelial cells during tooth germ morphogenesis. A reduction in Dpysl4 gene expression in the tooth germ produced a loss of ameloblasts, resulting in the decrease of synthesis and secretion of enamel.

Generation of a bioengineered tooth by using a three-dimensional cell manipulation method (organ germ method).

The arrangement of cells within a tissue plays an essential role in organogenesis, including tooth development. Organ morphogenesis and physiological functions induced by three-dimensional tissue organization are well known to be regulated by the proper spatiotemporal organization of various signaling molecules, including cytokines, extracellular matrix proteins, and adhesion molecules. Development of a three-dimensional cell manipulation technology to create a bioengineered organ germ, designated as the organ germ method, enabled the generation of a structurally correct and fully functional bioengineered tooth in vivo.

Functional tooth regeneration using a bioengineered tooth unit as a mature organ replacement regenerative therapy.

Donor organ transplantation is currently an essential therapeutic approach to the replacement of a dysfunctional organ as a result of disease, injury or aging in vivo. Recent progress in the area of regenerative therapy has the potential to lead to bioengineered mature organ replacement in the future. In this proof of concept study, we here report a further development in this regard in which a bioengineered tooth unit comprising mature tooth, periodontal ligament and alveolar bone, was successfully transplanted into a properly-sized bony hole in the alveolar bone through bone integration by recipient bone remodeling in a murine transplantation model system.