Quercetin Inhibits Orthodontic Tooth Movement-Associated Periodontitis by Regulating Macrophage Aerobic Glycolysis...

Orthodontic tooth movement (OTM) is frequently accompanied by inflammatory responses, including periodontitis, which may compromise treatment outcomes. This study investigated the protective role of quercetin, a natural flavonoid, in OTM-associated periodontitis and its underlying mechanism involving macrophage metabolic reprogramming via the IL-17/Hippo/YAP axis.

An in vivo OTM model was established using YAP-wild-type and YAP-knockout Sprague-Dawley rats to assess the effects of quercetin on periodontal inflammation and alveolar bone resorption. In vitro studies were conducted using the RAW264.7 macrophage cell line treated with quercetin (0.1-10 μM). Key methodologies included micro-CT analysis for alveolar bone loss, histopathological evaluation (H&E and TRAP staining), qPCR and western blot analysis for gene and protein expression, ELISA for cytokine quantification, flow cytometry for apoptosis and cell cycle analysis, and CCK-8 assays for cell viability. The role of YAP was further validated using specific inhibitors and genetic knockout models.

Quercetin administration significantly attenuated periodontal inflammation and alveolar bone loss in the OTM model. In RAW264.7 macrophages, quercetin suppressed IL-17-induced activation of the Hippo/YAP pathway, inhibited YAP nuclear translocation, and downregulated the expression of key glycolytic enzymes (HK2, LDHA, and PKM2). Consequently, quercetin reduced lactate production and aerobic glycolysis. These effects were reversed upon YAP overexpression, confirming the pivotal role of the IL-17/Hippo/YAP axis in quercetin-mediated metabolic modulation.

Quercetin alleviates OTM-associated periodontitis by inhibiting the IL-17/Hippo/YAP signaling pathway, thereby suppressing macrophage aerobic glycolysis. These findings highlight quercetin as a potential therapeutic adjunct in orthodontics to mitigate inflammatory complications.