Compressive force regulates GSK-313 in osteoclasts contributing to alveolar bone resorption during orthodontic tooth movement in vivo

Background: Orthodontic tooth movement mainly depends on biological and mechanical reactions in the periodontium, such as the indispensable reconstruction process of the periodontal ligament and alveolar bone. To explore whether orthodontic compressive force can induce bone resorption during orthodontic tooth movement by regulating the GSK-313/13-catenin pathway.Methods: We established orthodontic tooth movement models in Sprague-Dawley rats. In addition, compressive force-induced bone resorption that occurred during orthodontic tooth movement was analyzed by HE staining and micro-CT. The number and distribution of osteoclasts were observed by TRAP staining. Furthermore, pressureinduced bone resorption mediated by the GSK-313/13-catenin signaling pathway was analyzed by immunohistochemistry.Results: As shown by the micro-CT results, bone parameters, such as bone mineral density (BMD), the bone volume fraction (BV/TV), and trabecular thickness (Tb. Th), were significantly decreased under orthodontic compressive force stimulation, in contrast with the dramatically increased trabecular spacing (Tb. Sp). During the process of tooth movement, the compressive force can induce bone resorption on the side with the force, which increases the expression of phosphorylated Ser-GSK-313 and activation of the 13-catenin signaling pathway. Additionally, downregulation of the GSK-313 activity further caused the downregulation of bone parameters, leading to bone loss. The TRAP staining and immunohistochemistry staining results indicated that orthodontic compressive force influenced osteoclast formation and the secretion of osteoclast-related cytokines, matrix metallopeptidase 9 (MMP-9) and receptor activator of nuclear factor-xB ligands (RANKLs), which is also related to the duration of orthodontic force.Conclusions: These results indicated that the GSK-313 inhibitor can promote osteoclast formation on the side with orthodontic compressive force. In addition, the activation of the GSK-313/13-catenin signaling pathway contributes to bone reconstruction caused by orthodontic compressive force. Therefore, the GSK-313/13-catenin signaling pathway can be a potential target for further clinical applications.