Tomokazu Yoshino

Notch Signaling Induces Root Resorption via RANKL and IL-6 from hPDL Cells

In this study, we first investigated the expressions of Jagged1, Notch2, the receptor activator of nuclear factor–kappa B ligand (RANKL), and interleukin (IL)-6 in areas of root resorption during experimental tooth movement in rats in vivo. We then assessed the effects of compression force (CF) with or without GSI (an inhibitor of Notch signaling) on Jagged1, RANKL, and IL-6 release from human periodontal ligament (hPDL) cells. Twelve male 6-wk-old Wistar rats were subjected to an orthodontic force of 50 g to induce mesially tipping movement of the upper first molars for 7 d. The expression levels of tartrate-resistant acid phosphatase, Jagged1, Notch2, IL-6, and RANKL proteins in the dental root were determined using an immunohistochemical analysis. Furthermore, the effects of the CF on Jagged1, IL-6, and RANKL production were investigated using hPDL cells in vitro. The effects of the cell-conditioned medium obtained from the hPDL cells subjected to CF (CFM) and Jagged 1 on osteoclastogenesis of human osteoclast precursor cells (hOCPs) were also investigated. Under the conditions of experimental tooth movement in vivo, resorption lacunae with multinucleated cells were observed in the 50 g group. In addition, immunoreactivity for Jagged1, Notch2, IL-6, and RANKL was detected on day 7 in the PDL tissue subjected to the orthodontic force. In the in vitro study, the compression force increased the production of Jagged1, IL-6, and RANKL from the hPDL cells, whereas treatment with GSI inhibited the production of these factors in vitro. The osteoclastogenesis increased with the CFM and rhJagged1, and the increase in the osteoclastogenesis was almost inhibited by GSI. These results suggest that the Notch signaling response to excessive orthodontic forces stimulates the process of root resorption via RANKL and IL-6 production from hPDL cells.

Interleukin-17 is involved in orthodontically induced inflammatory root resorption in dental pulp cells

INTRODUCTION The objectives of this study were (1) to investigate the expressions of interleukin (IL)-17, RANKL (the receptor activator of NF-kappaB ligand), and osteoprotegerin (OPG) in root resorption areas during experimental tooth movement in rats, and (2) to determine the effect of IL-17 on the expressions of RANKL and OPG mRNA from human dental pulp cells. METHODS Twelve male 6-week-old Wistar rats were subjected to an orthodontic force of 50 g to induce a mesially tipping movement of the maxillary first molars for 7 days. The expression levels of tartrate resistant acid phosphatase (TRAP), interleukin (IL)-17, IL-17 receptor (IL-17R), receptor activator of nuclear factor-kappa B ligand (RANKL), and OPG proteins were determined in dental pulp by immunohistochemical analysis. Furthermore, the effects of IL-17 on the expressions of RANKL and OPG mRNA were investigated using human dental pulp cells in vitro. RESULTS In the experimental tooth movements in vivo, resorption lacunae with multinucleated cells were observed in the 50-g group. The immunoreactivities for IL-17, IL-17R, and RANKL were detected in dental pulp tissues subjected to the orthodontic force on day 7. Moreover, IL-17 increased the mRNA expression of RANKL from human dental pulp cells in vitro. CONCLUSIONS The results of this study suggest that IL-17 and RANKL may be involved in the process of orthodontically induced inflammatory root resorption in dental pulp cells.

Notch signaling induces root resorption via RANKL and IL-6 from hPDL cells

The Notch signaling plays an important role in osteoblast and osteoclast differentiation. However, the role of Notch signaling in root resorption during orthodontic treatment is not yet fully understood. In this study, we first investigated the expressions of Jagged1, RANKL and IL-6 in areas of root resorption during experimental tooth movement in rats in vivo. We then assessed the effects of compression forces (CF) with/without GSI (an inhibitor of Notch signaling)on Jagged1,RANKL, and IL-6release from human periodontal ligament (hPDL) cells. Twelve male Wistar rats were subjected to an orthodontic force of 50 g in order to induce mesially tipping movement of the upper first molars for 7 days. The expression levels of TRAP, Jagged1, Notch2, RANKL and IL-6 proteins in the dental root were determined using an immunohistochemical analysis. Furthermore, the effects of the CF on Jagged1, RANKL and IL-6 production were investigated using hPDL cells in vitro. The effects of the cell-conditioned medium obtained from the hPDL cells subjected to CF (CFM) and Jagged1 (rhJagged1) on osteoclastogenesis of human osteoclast precursor cells (hOCPs) also investigated. Under theconditions of experimental tooth movement in vivo, resorption lacunae with multinucleated cells were observed in the 50 g group. In addition, immunoreactivity for TRAP, Jagged1, Notch2, RANKL and IL-6 was detected on day 7 in the PDL tissue subjected to the orthodontic force. In the in vitro study, the compression force increased the production of Jagged1, RANKL and IL-6 from the hPDL cells, while treatment with GSI inhibited the production of RANKL and IL-6 in vitro. The osteoclastogenesis increased by the CFM and rhJagged1, and the increase in the osteoclastogenesis was almost inhibited by GSI. These results suggest that the Notch signaling response to excessive orthodontic forces stimulates the process of root resorption via RANKL and IL-6 production from hPDL cells.