IL-33 accelerates orthodontic tooth movement by promoting M1 differentiation of macrophages and osteoclast formation

Developing methods to promote tooth movement can help reduce the duration of orthodontic treatment for patients. A mouse model of orthodontic tooth movement (OTM) was established to analyze the key role of the IL-33/ST2 signaling pathway in this process. Human periodontal ligament fibroblasts (hPDLFs) and human CD14⁺ monocytes were isolated to investigate the effect of IL-33/ST2 signaling on directed cell differentiation. Orthodontic mechanical force induced the protein expression of IL-33 and ST2 in periodontal tissues. Injection of recombinant mouse IL-33 protein (10 µl, 10 µg/mL, every other day) accelerated tooth movement, increased the proportion of proinflammatory macrophages (CD45⁺CD11b⁺F4/80⁺Ly6C⁺), decreased the proportion of reparative macrophages (CD45⁺CD11b⁺F4/80⁺CD206⁺), and upregulated the expression of cathepsin K in periodontal tissues. In contrast, injection of anti-mouse ST2 antibody (10 µl, 100 µg/mL, every other day) exerted the opposite effects. THRA was identified as a transcriptional activator of IL-33 in hPDLFs, and its expression was also induced by orthodontic mechanical force. Additionally, the IL-33/ST2 signaling pathway promoted osteoclast differentiation of human monocytes. IL-33 accelerates OTM by promoting M1 differentiation of macrophages and osteoclast formation.