Notch signaling inhibition protects against root resorption in experimental immature tooth movement in rats

Abstract

This study aimed to build an experimental immature tooth movement model and verify less resorption of incompletely developed roots than those fully developed during the same orthodontic treatment, followed by investigating the cellular and molecular mechanism. The development of Wistar rat tooth was investigated using invivo microcomputed tomography and hematoxylin and eosin staining to decide the optimal ages of rats for immature tooth and mature tooth groups. The rats in the immature tooth and mature tooth groups were divided into experimental, sham control, and blank control groups. After orthodontic treatment for 3weeks, the mesial root volume, crown movement distance, neck movement distance, root inclination, and apical distance were measured by microcomputed tomography. The expressions of TRAP, Jagged1, Notch2, IL-6, and RANKL were analyzed by immunohistochemical staining and real-time polymerase chain reaction. The repair of root resorption was also investigated after removing orthodontic force for 3 and 6weeks. The root achieved the development stage around 10weeks, so 4-week-old rats and 10-week-old rats were used in the immature tooth group and mature tooth group, respectively. The volume of root resorption in the experimental immature tooth group was 0.0869±0.0244mm3, which was less than that in the mature tooth group (0.1218±0.0123mm3)(P<0.001). Immature tooth movement decreased TRAP-positive odontoclasts on the compression side while having no statistically significant effect on osteoclasts. The protein expression of Jagged1, Notch2, IL-6, and RANKL in the mature tooth group increased significantly compared with the immature tooth group, not only on the compression side but also on the tension sides. The mRNA expression of Jagged1, Notch2, and RANKL was significantly lower in the immature tooth group, whereas the expression of IL-6 had no significance but a strong tendency. The root volume after repairing for 3weeks was still less than that of blank control, whereas after repairing for 6weeks, the difference was not statistically significant. The experimental immature tooth movement model for the Wistar rat was achieved for the first time. The immature tooth will suffer less root resorption than the mature tooth, which may be due to odontoclastogenesis inhibition by decreased expression of Jagged1/Notch2/IL-6/RANKL signaling.