The Rho-mDia1 signaling pathway is required for cyclic strain-induced cytoskeletal rearrangement of human periodontal ligament cells

• Cyclic strain increased the binding of RhoA-GTP with mDia1.
• Silencing of mDia1 decreased the cytoskeletal rearrangement of hPDLCs.
• Rho-GDIa regulated the expression of RhoA-GTP, mDia1, and profilin-1 protein.
• Rho-GDIa regulated the cytoskeletal rearrangement of hPDLCs induced by cyclic strain.

Tooth movement is the result of periodontal tissue reconstruction. The biomechanical effects produced by orthopedic forces can affect the cytoskeletal rearrangement of human periodontal ligament cells (hPDLCs). However, the mechanisms responsible for the cytoskeletal rearrangement are not completely understood. To analyze the effect, we investigated the role of the Rho-mDia1 signaling pathway in cyclic strain-induced cytoskeletal rearrangement of hPDLCs in detail. We cultured hPDLCs on collagen I-coated six-well Bioflex plates and then exposed them to cyclic strain with physiological loading (10%) at a frequency of 0.1 Hz for 6 or 24 h using a Flexercell Tension Plus system. Notably, the cells cultured on the Bioflex plates showed increased expression levels of RhoA-GTP, profilin-1 protein, and the combination of RhoA and mDia1, whereas the expression levels of Rho-GDIa were reduced compared with a static control group. Furthermore, the cytoskeletal rearrangement of cells was enhanced. However, profilin-1 protein expression and cytoskeletal reorganization under cyclic strain can decrease due to the overexpression of Rho-GDIa or mDia1-siRNA transfection, whereas Rho-GDIa siRNA transfection has the opposite effect on hPDLCs. Together, our results demonstrate that the Rho-mDia1 signaling pathway is involved in the cytoskeletal rearrangement of hPDLCs induced by cyclic strain. These observations may enable a more in-depth understanding of orthodontic tooth movement and the reconstruction of PDL and alveolar bone.