Compressive force-induced succinate production via metabolic reprogramming in periodontal ligament cells promotes orthodontic tooth movement.

OBJECTIVE: This study aimed to elucidate metabolic alterations in gingival crevicular fluid (GCF) during orthodontic tooth movement (OTM) and investigate the role of the succinate-SUCNR1 axis in bone resorption and tooth movement. RESULTS: OTM was accompanied by the change of TCA cycle and increase of succinate in the human GCF. Succinate accumulation was observed in periodontal ligament cells (PDLCs) under compressive force, accompanied by increase of glycolysis and decrease of succinic dehydrogenase activity. Suppression of the succinate-SUCNR1 axis reduced osteoclastogenesis in BMDMs. OTM slowed down in the SUCNR1(-)/(-) mice when compared with wild mice. CONCLUSION: OTM is accompanied by the increase of succinate in periodontal tissues. Compressive force induces metabolic reprogramming in PDLCs, leading to enhanced succinate production. Succinate promotes macrophage migration and osteoclast differentiation via the SUCNR1 axis, ultimately facilitating orthodontic tooth movement. These findings provide a new potential therapeutic target for regulating periodontal tissue remodeling during orthodontic treatment.