Effect of Metformin on Inflammatory Response in Periodontitis Mice by Regulating the TLR4/NF-κB Signaling Pathway

This study aims to investigate the effect of MET (metformin) on the inflammatory response in periodontitis mice by regulating the TLR4 (Toll-like receptor 4)/NF-κB (nuclear factor-κB) signaling pathway. A periodontitis mouse model was constructed and the mice were separated into Control group, Model group, low, medium, and high dose metformin groups (MET-L group, MET-M group, MET-H group), and high-dose metformin+TLR4 activator group (MET-H+LPS group). The pathological changes of periodontal tissue in mice were observed by Micro-CT and HE staining. The mRNA expression levels of IL-1β (interleukin-1β), IL-6 (inter leukin-6), and TNF-α (tumor necrosis factor-α) in periodontal tissue were detected by qRT-PCR. The expression of RANKL (receptor activator of nuclear factor-κB ligand) and OPG (osteoprotegerin) in periodontal tissue was detected by immunohistochemistry. The expression of TLR4/NF-κB pathway-associated proteins was detected by Western blot. Compared with the Control group, the alveolar bone of mice in the Model group showed ob vious absorption, with a larger bone absorption area, more severe periodontal lesions, and a large amount of inflammatory cell infiltration; the IL-1β, IL-6, TNF-α mRNA, and TLR4, p-NF-κB/NF-κB, RANKL expression levels increased, while OPG expression level decreased (P<0.05). Compared with the Model group, the MET L, MET-M, and MET-H groups showed a gradual decrease in alveolar bone resorption, reduced infiltration of inflammatory cells, and gradual relief of periodontal lesions; the TNF-α, IL-6, and IL-1β mRNA levels gradually decreased in a dose-dependent manner, the TLR4, p-NF-κB/NF-κB, and RANKL expression levels decreased, while the OPG expression level increased (P<0.05). Compared with the MET-H group, the MET-H+LPS group showed increased alveolar bone resorption, larger bone resorption areas, and more inflammatory cell infiltration; the TNF-α, IL-6, IL-1β mRNA, and TLR4, p-NF-κB/NF-κB, RANKL expression levels increased, while OPG expression level decreased (P<0.05). Metformin inhibits the TLR4/NF-κB signaling pathway and improves the inflammatory response in periodontitis mice.

CSTR: 32200.14.cjcb.2024.09.0007