Zhu Yanlin, Qiao Shuwei, Pang Yuxuan, Wang Huimin, Zhou Yanmin
Department of Dental Implantology, Hospital of Stomatology, Jilin University, Changchun, People's Republic of China.
Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, Hospital of Stomatology, Jilin University, Changchun, People's Republic of China.
J Inflamm Res. 2024 Nov 25;17:9637-9650. doi: 10.2147/JIR.S490823. eCollection 2024.
Although the anti-inflammatory properties of the hypoxia-mimetic drug deferoxamine (DFO) have been reported, its potential as a treatment for periodontitis remains unknown. This study investigated the therapeutic benefits of DFO on osteoclastogenesis and inflammation in periodontitis progression.
RAW264.7 cells were pretreated with DFO before stimulation with lipopolysaccharides from (-LPS). Hypoxia-inducible factor-1α (HIF-1α) and inflammatory factors were measured, followed by analysis of relevant inflammatory pathways. Immunofluorescence and molecular biology methods were employed to assess osteoclast differentiation in RAW264.7 cells after nuclear factor-κB ligand (RANKL) induction. A rat model of periodontitis was es\lished using ligature wires, and alveolar bone loss was assessed via micro-computed tomography. Osteoclastogenesis and periodontal inflammation were assessed through immunohistochemistry as well as hematoxylin and eosin staining.
DFO reduced the -LPS-induced inflammatory factor expression ( < 0.0001) and upregulated HIF-1α ( = 0.0278) in RAW264.7 cells. DFO suppressed NF-κB signaling by inhibiting NF-κB p65 nuclear translocation and phosphorylation. DFO pretreatment inhibited osteoclast development by decreasing F-actin rings synthesis, reducing the number of mature osteoclasts ( < 0.0001) and downregulating osteoclast-specific markers ( < 0.05). In rat periodontitis models, DFO treatment reduced tissue inflammation, osteoclastogenesis, and alveolar bone loss ( < 0.05).
DFO effectively prevented osteoclast development, alveolar bone loss, and inflammation associated with periodontitis.
尽管已有报道称缺氧模拟药物去铁胺（DFO）具有抗炎特性，但其作为牙周炎治疗药物的潜力仍不明确。本研究调查了DFO在牙周炎进展过程中对破骨细胞生成和炎症的治疗作用。
在用来自牙龈卟啉单胞菌的脂多糖（-LPS）刺激之前，用DFO预处理RAW264.7细胞。测量缺氧诱导因子-1α（HIF-1α）和炎症因子，随后分析相关炎症途径。采用免疫荧光和分子生物学方法评估核因子-κB配体（RANKL）诱导后RAW264.7细胞中的破骨细胞分化。使用结扎丝建立大鼠牙周炎模型，并通过微型计算机断层扫描评估牙槽骨吸收。通过免疫组织化学以及苏木精和伊红染色评估破骨细胞生成和牙周炎症。
DFO降低了-LPS诱导的RAW264.7细胞中炎症因子的表达（<0.0001），并上调了HIF-1α（=0.0278）。DFO通过抑制NF-κB p65核转位和磷酸化来抑制NF-κB信号传导。DFO预处理通过减少F-肌动蛋白环合成、减少成熟破骨细胞数量（<0.0001）和下调破骨细胞特异性标志物（<0.05）来抑制破骨细胞发育。在大鼠牙周炎模型中，DFO治疗减少了组织炎症、破骨细胞生成和牙槽骨吸收（<0.05）。
DFO有效预防了与牙周炎相关的破骨细胞发育、牙槽骨吸收和炎症。
