The role of EphB4/ephrinB2 signaling in root repair after orthodontically-induced root resorption

Abstract

This study aimed to investigate the effect of EphB4/ephrinB2 signaling on orthodontically-induced root resorption repair and the possible molecular mechanism behind it. Seventy-two 6-week-old male Wistar rats were randomly divided into 3 groups: blank control group, physiological regeneration group (PHY), and EphB4 inhibitor local injection group (INH). A root repair model was built on experimental rats of the PHY and INH groups. The animals in the INH groups received a daily periodontal local injection of EphB4 inhibitor NVP-BHG712, whereas the blank control group and PHY groups received only the vehicle. Histologic staining and microcomputed tomography analysis showed that root regeneration was inhibited in the INH group compared with the PHY group with a greater number of osteoclasts. Immunohistochemical staining showed active EphB4/ephrinB2 signaling activities during root regeneration. The cementogenesis-related factors cementum attachment protein, alkaline phosphatase, osteopontin, and runt-related transcription factor 2, and osteoclastic-related factors RANKL and osteoprotegerin were affected by regulated EphB4/ephrinB2 signaling. These findings demonstrated that the EphB4/ephrinB2 signaling might be a promising therapeutic target for novel therapeutic approaches to reduce orthodontically-induced root resorption through enhancement of cementogenesis.