IADR Abstract Archives
Notch Signaling Exacerbates Orthodontic Root Resorption by Suppressing Wnt Signaling
Objectives: Orthodontically induced inflammatory root resorption (OIIRR) is accidental symptom in orthodontic treatment. Notch and Wnt signaling pathway plays an important role in bone metabolism. However, the role of these signalings in tooth movement and root resorption in orthodontic treatment has not fully understood.
The objective is to elucidate, the mechanism of occurrence of OIIRR. We examined the effects of orthodontic force on Notch and Wnt expression in human periodontal ligament (hPDL) cells in vitro, and the expression of Jagged1, Notch2, RANKL and IL-6 in root resorption area during experimental tooth movement in rats.
Methods: In vivo study, rats were subjected to an orthodontic force of 50 g 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. In vitro study, compression forces (CF) were applied to hPDL cells with/without γ-secretase inhibitor (GSIb;binhibitor of Notch signaling) for up to 24 hours (CF group, CF+GSI group). Moreover, hPDL cells were stimulated by Wnt5a (100ng) for up to 24 hours. The expression of Jagged1, Wnt5a, RANKL, IL-6, COL1 and ALP mRNA and protein were determined by using by real-time PCR and ELISA.
Results: On days 7, immunoreactivity for Jagged1, Notch2, RANKL and IL-6 was detected in 50 g group. In the CF group, the mRNA and protein expression of Jagged1, RANKL and IL-6 were increased. In contrast, Wnt5a production were decreased. In the CF+GSI group, the mRNA and protein expression of Jagged1, RANKL and IL-6 were decreased, while the production of wnt5a were increased. Stimulation with Wnt5a increased the levels of COL1 and ALP mRNA expression from hPDL cells.
Conclusions: These results suggest that the Notch signaling response to excessive orthodontic forces suppresses Wnt signaling from hPDL cells, and exacerbates orthodontic root resorption.
The objective is to elucidate, the mechanism of occurrence of OIIRR. We examined the effects of orthodontic force on Notch and Wnt expression in human periodontal ligament (hPDL) cells in vitro, and the expression of Jagged1, Notch2, RANKL and IL-6 in root resorption area during experimental tooth movement in rats.
Methods: In vivo study, rats were subjected to an orthodontic force of 50 g 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. In vitro study, compression forces (CF) were applied to hPDL cells with/without γ-secretase inhibitor (GSIb;binhibitor of Notch signaling) for up to 24 hours (CF group, CF+GSI group). Moreover, hPDL cells were stimulated by Wnt5a (100ng) for up to 24 hours. The expression of Jagged1, Wnt5a, RANKL, IL-6, COL1 and ALP mRNA and protein were determined by using by real-time PCR and ELISA.
Results: On days 7, immunoreactivity for Jagged1, Notch2, RANKL and IL-6 was detected in 50 g group. In the CF group, the mRNA and protein expression of Jagged1, RANKL and IL-6 were increased. In contrast, Wnt5a production were decreased. In the CF+GSI group, the mRNA and protein expression of Jagged1, RANKL and IL-6 were decreased, while the production of wnt5a were increased. Stimulation with Wnt5a increased the levels of COL1 and ALP mRNA expression from hPDL cells.
Conclusions: These results suggest that the Notch signaling response to excessive orthodontic forces suppresses Wnt signaling from hPDL cells, and exacerbates orthodontic root resorption.