Abstract：
OBJECTIVE: The aim of this study was to investigate the effect of 4μ8c, an inhibitor targeting the endoplasmic reticulum stress-associated factor IRE1α, on macrophage polarization in an experimental model of diabetic periodontitis through ex vivo experiments.
METHODS: Local alveolar bone parameters were evaluated using Micro-CT following intraperitoneal administration of 4μ8c in mice with experimental diabetic periodontitis. Surface markers indicating macrophage polarization were identified using immunofluorescence. In vitro experiments were performed employing bone marrow-derived macrophages and gingival fibroblasts. Macrophage polarization was determined using flow cytometry. Principal impacted signaling pathways were identified through Western blot analysis.
RESULTS: Results from both in vitro and in vivo experiments demonstrated that 4μ8c mitigated alveolar bone resorption and inflammation in mice with diabetic periodontitis. Furthermore, it modulated macrophage polarization towards the M2 phenotype and augmented M2 macrophage polarization through the MAPK signaling pathway.
CONCLUSIONS: These findings suggest that inhibiting IRE1α can modulate macrophage polarization and alleviate ligature-induced diabetic periodontitis via the MAPK signaling pathway. This unveils a novel mechanism, offering a scientific foundation for the treatment of experimental diabetic periodontitis.
METHODS: Local alveolar bone parameters were evaluated using Micro-CT following intraperitoneal administration of 4μ8c in mice with experimental diabetic periodontitis. Surface markers indicating macrophage polarization were identified using immunofluorescence. In vitro experiments were performed employing bone marrow-derived macrophages and gingival fibroblasts. Macrophage polarization was determined using flow cytometry. Principal impacted signaling pathways were identified through Western blot analysis.
RESULTS: Results from both in vitro and in vivo experiments demonstrated that 4μ8c mitigated alveolar bone resorption and inflammation in mice with diabetic periodontitis. Furthermore, it modulated macrophage polarization towards the M2 phenotype and augmented M2 macrophage polarization through the MAPK signaling pathway.
CONCLUSIONS: These findings suggest that inhibiting IRE1α can modulate macrophage polarization and alleviate ligature-induced diabetic periodontitis via the MAPK signaling pathway. This unveils a novel mechanism, offering a scientific foundation for the treatment of experimental diabetic periodontitis.
摘要：
目的：本研究的目的是研究4μ8c的作用，一种靶向内质网应激相关因子IRE1α的抑制剂，通过离体实验研究糖尿病牙周炎实验模型中的巨噬细胞极化。
方法：在实验性糖尿病性牙周炎小鼠中腹膜内施用4μ8c后，使用Micro-CT评估局部牙槽骨参数。使用免疫荧光鉴定指示巨噬细胞极化的表面标志物。使用骨髓来源的巨噬细胞和牙龈成纤维细胞进行体外实验。使用流式细胞术确定巨噬细胞极化。通过蛋白质印迹分析鉴定主要受影响的信号传导途径。
结果：体外和体内实验的结果表明，4μ8c减轻了糖尿病性牙周炎小鼠的牙槽骨吸收和炎症。此外，它通过MAPK信号通路调节巨噬细胞向M2表型的极化，并增强M2巨噬细胞的极化。
结论：这些发现表明，抑制IRE1α可以通过MAPK信号通路调节巨噬细胞极化，减轻结扎诱导的糖尿病牙周炎。这揭示了一种新颖的机制，为实验性糖尿病性牙周炎的治疗提供科学依据。
方法：在实验性糖尿病性牙周炎小鼠中腹膜内施用4μ8c后，使用Micro-CT评估局部牙槽骨参数。使用免疫荧光鉴定指示巨噬细胞极化的表面标志物。使用骨髓来源的巨噬细胞和牙龈成纤维细胞进行体外实验。使用流式细胞术确定巨噬细胞极化。通过蛋白质印迹分析鉴定主要受影响的信号传导途径。
结果：体外和体内实验的结果表明，4μ8c减轻了糖尿病性牙周炎小鼠的牙槽骨吸收和炎症。此外，它通过MAPK信号通路调节巨噬细胞向M2表型的极化，并增强M2巨噬细胞的极化。
结论：这些发现表明，抑制IRE1α可以通过MAPK信号通路调节巨噬细胞极化，减轻结扎诱导的糖尿病牙周炎。这揭示了一种新颖的机制，为实验性糖尿病性牙周炎的治疗提供科学依据。
