Contribution of diabetes mellitus to periodontal inflammation during orthodontic tooth movement

Objective This study aims to clarify the effects of diabetes mellitus (DM) on inflammatory profile during orthodontic tooth movement (OTM) and explore potential mechanisms. Methods OTM models were established in healthy (Ctrl) and DM rats for 0, 3, 7 or 14 days. The tooth movement distance and bone structural parameters were analyzed through micro-CT. The bone resorption activity and periodontal inflammation status were evaluated through histological staining. RNA sequencing was performed to detect differentially expressed genes in force loading-treated periodontal ligament fibroblasts (PDLFs) with or without high glucose. The differential expression of inflammatory genes associated with NOD-like receptor family pyrin domain containing 3 (NLRP3) between groups was tested in vitro and in vivo. Results DM caused remarkable reduction of alveolar bone height and density around the moved tooth, corresponding with the higher bone resorption activity and inflammatory scores of DM group. For force loading-treated PDLFs, high glucose induced the activation of inflammatory pathways, including NLRP3. Elevated expression of NLRP3 and cascade molecules (Caspase-1, GSDMD, and IL-1 beta) were validated by RT-qPCR, Western blot, and immunohistochemistry staining. Conclusions DM alters the inflammatory status of periodontium and affects tissue reconstruction during OTM. NLRP3 inflammasome may involve in diabetes-induced periodontal changes.