Autophagy of periodontal ligament inhibits inflammation and reduces the decline of bone density during orthodontic tooth movement of mice

Objective: Autophagy can respond to compressive force and involves in bone remodeling and inflammation adjustment. The aim of this study was to investigate the role of the autophagy of periodontal ligament in the regulation of orthodontic tooth movement (OTM) and inflammation that is caused by orthodontic force. Methods: C57BL/6 mice were selected and divided into control group (Control), OTM group (OTM), OTM + autophagy inhibitor 3-Methyladenine group (OTM+3-MA), and OTM autophagy promoter rapamycin group (OTM + RAPA). 3-MA or rapamycin was injected intraperitoneally daily. After 7 days of OTM, the mice were sacrificed and the maxillae were taken. Micro-CT was used to detect OTM distance and bone density. HE staining was applied to observe the structure of the periodontal ligament. qPCR and Immunohistochemistry were utilized to detect the inflammation of peridentium. Results: The inhibition of autophagy accelerated OTM, downregulated bone density, and made the structure of the periodontal ligament more disordered, while the improvement of autophagy had reverse results in OTM. Inflammation-related genes, such as Il-1, Il-6, and Tnf-alpha increased after OTM and displayed the highest expression in the OTM+3-MA group. Immunohistochemistry illustrated that the expression of IL-6 was higher in the OTM group and the OTM+3-MA group. Conclusions: The increase of autophagy can reduce the decline of bone density, inhibit the expression of inflammatory factors, and arrange the periodontal ligament during OTM, thus providing a new way for the effective regulation of inflammation in clinical orthodontic treatment, so as to achieve more efficient and healthier tooth movement.