Mechanisms of sphingosine-1-phosphate (S1P) signaling on excessive stress-induced root resorption during orthodontic molar intrusion.

Abstract

The aim of this study was to investigate cementocyte mechanotransduction during excessive orthodontic intrusive force-induced root resorption and the role of S1P signaling in this process. Fifty-four 12-week-old male Wistar rats were randomly divided into 3 groups: control group (Control), intrusive stress application group (Stress), and intrusive stress together with S1PR2-specific antagonist injection group (Stress + JTE). A rat molar intrusion model was established on animals in the Stress and the Stress + JTE groups. The animals in the Stress + JTE group received daily intraperitoneal (i.p.) injection of S1PR2 antagonist JTE-013, while the Control and Stress groups received only the vehicle. Histomorphometric, immunohistochemical, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses were performed after euthanizing of the rats. Root resorption was promoted in the Stress group with increased volumes of resorption pits and amounts of molar intrusion compared with the Control group. The expression levels of cementogenic- and cementoclastic-related factors were affected under excessive intrusive force. Immunohistochemical staining and qRT-PCR analysis showed promoted S1P signaling activities during molar intrusion. Western blot analysis indicated decreased nuclear translocation of β-catenin under excessive intrusive force. Through the administration of JTE-013, S1P signaling activity was suppressed and excessive intrusive force-induced root resorption was reversed. The regulation of S1P signaling could also influence the nuclear translocation of β-catenin and the expressions of cementogenic- and cementoclastic-related factors. Root resorption was promoted under excessive orthodontic intrusive force due to the disruption of cementum homeostasis. S1P signaling pathway might play an important role in cementocyte mechanotransduction in this process. The S1P signaling might be a promising therapeutic target for novel therapeutic approaches to prevent external root resorption caused by excessive orthodontic intrusive force.