Protective roles of FICZ and aryl hydrocarbon receptor axis on alveolar bone loss and inflammation in experimental periodontitis
Protective roles of FICZ and aryl hydrocarbon receptor axis on alveolar bone loss and inflammation in experimental periodontitis
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FICZ和芳烃受体轴对实验性牙周炎牙槽骨丢失和炎症的保护作用
DOI：
10.1111/jcpe.13166
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发表时间：
2019-09-01
影响因子：
6.7
通讯作者：
Wang, Yining
中科院分区：
文献类型：
--
作者：
Huang, Jing;Cai, Xinjie;Wang, Yining
目的芳烃受体（AhR）-配体轴参与炎症性疾病和骨稳态的调节。然而，AhR信号通路的激活和AhR配体在牙周炎中的可能功能尚不清楚。本研究探讨了AhR靶基因细胞色素P450亚家族B成员1（CYP 1B 1）在牙周炎中的表达及AhR配体6-甲酰吲哚并[3，2-B]咔唑（FICZ）在牙周炎中的作用和机制。材料与方法检测人牙周炎标本、结扎性牙周炎模型及脂多糖（LPS）诱导的牙周膜细胞（PDLCs）中CYP 1B 1的表达。FICZ局部或全身给药。通过qPCR、显微CT和免疫组化检测FICZ的治疗作用。最后，AhR信号在牙周炎的机制进行了研究，通过细胞分析。结果CYP 1B 1在牙周炎中表达下调。FICZ可减轻牙周炎小鼠牙槽骨丢失，减轻炎症因子。在体外，FICZ预处理通过增加STAT 3的磷酸化减少了PDLC中LPS诱导的炎症。此外，FICZ通过激活Wnt/β-连环蛋白信号通路促进PDLCs的矿化。结论牙周炎时AhR信号通路受到抑制，AhR配体FICZ对牙周炎有预防作用。
Aim The aryl hydrocarbon receptor (AhR)-ligand axis has been shown to be involved in inflammatory diseases and bone homeostasis. However, the activation of AhR signalling pathway and the possible functions of AhR ligands in periodontitis are underexplored. This study investigated the expression of the AhR target gene cytochrome P450 subfamily B member 1 (CYP1B1) and the functions and mechanisms of the AhR ligand 6 formylindolo[3,2-b]carbazole (FICZ) in periodontitis. Materials and Methods CYP1B1 expression was detected in human periodontitis samples, mice with ligature-induced periodontitis and lipopolysaccharide (LPS)-induced inflammation in periodontal ligament cells (PDLCs) in vitro. FICZ was administered topically or systemically. The therapeutic functions of FICZ were detected via qPCR, micro-computed tomography and immunohistochemistry. Finally, the mechanisms of AhR signalling in periodontitis were investigated by cell assays. Results CYP1B1 expression was downregulated in periodontitis. FICZ rescued the alveolar bone loss and mitigated the inflammatory cytokines in periodontitis mice. In vitro, FICZ pre-treatment reduced the LPS-induced inflammation in PDLCs via the increased phosphorylation of STAT3. Additionally, FICZ prompted the mineralization of PDLCs via activation of the Wnt/beta-catenin signalling pathway. Conclusion AhR signalling pathway is suppressed in periodontitis and the AhR ligand FICZ can prevent periodontitis.