Tensile force promotes osteogenic differentiation via ephrinB2-EphB4 signaling pathway in orthodontic tooth movement

In orthodontic treatment, alveolar bone remodeling is the basis of tooth movement, therefore, exploring the impact of mechanical force on bone remodeling and related signaling pathways are of great importance. EphrinB2-EphB4 bidirectional signaling plays an important role in communication between osteoblasts and osteoclasts. However, whether ephrinB2-EphB4 signaling is involved in the osteogenic differentiation promoted by tensile force (TF) is unclear. Therefore, in this study, we first explored the effect of TF on osteogenic differentiation in cells, and found that TF significantly increased the expression levels of RUNX2, OPN and EphB4 in MC3T3-E1 cells, but when ephrinB2-EphB4 signaling was blocked by NVP-BHG712, TF-induced promotion of osteogenic differentiation was inhibited. Then we established a rat orthodontic tooth movement (OTM) model, through Micro CT and H&E staining, we found that TF improved alveolar bone formation through ephrinB2-EphB4 signaling.MAPK members are involved in osteogenic differentiation, and we found that TF promoted the expression of p-ERK1/2, p-P38 and p-JNK1/2/3. When EphB4 receptor was blocked, the expression of p-ERK1/2 promoted by TF was decreased, and it was the downstream pathway of ephrinB2-EphB4 signaling that mediates TF-induced promotion of osteogenic differentiation in MC3T3-E1 cells.