关键词: 牙周炎, ATF6, 巨噬细胞, 骨吸收, 炎症反应

Abstract:

Objective To investigate the role of activating transcription factor 6(ATF6) in macrophage-mediated periodontal inflammation and alveolar bone resorption. Methods An inflammation model was established by stimulating RAW264.7 cells with lipopolysaccharide (LPS). RT-qPCR was used to detect changes in the expression of inflammatory factors and ATF6. The function of ATF6 was further validated using siRNA knockdown. Macrophage-specific ATF6 knockout mice(ATF6^fl/fl; Cx3cr1^CreERT2) were generated. Experimental periodontitis was induced using the silk ligature method. Alveolar bone resorption and inflammation levels were evaluated by Micro-CT, HE staining, and bone morphometric analysis. Results As shown in experiments, LPS stimulation significantly upregulated ATF6 expression in macrophages and markedly increased the level of inflammatory. Knockdown of ATF6 significantly inhibited the expression of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in LPS-induced macrophages. Consistently, studies demonstrated that macrophage-specific deletion of ATF6 notably attenuated alveolar bone loss induced by periodontitis and improved the bone volume fraction(BV/TV). Conclusion Macrophage-derived ATF6 plays a critical pro-inflammatory role in the progression of periodontitis. Reduction of its expression attenuates inflammatory responses and alveolar bone resorption.

Key words: periodontitis, ATF6, macrophages, bone resorption, inflammatory response