State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China; Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Peking University, Beijing, China.
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
Arch Oral Biol. 2018 Jan;85:16-22. doi: 10.1016/j.archoralbio.2017.10.004. Epub 2017 Oct 7.
Pulpitis is a multi-factorial disease that could be caused by complex interactions between genetics, epigenetics and environmental factors. We aimed to evaluate the role of Enhancer of Zeste Homolog 2 (EZH2) in the inflammatory response of human dental pulp cells (HDPCs) and dental pulp tissues.
The expressions of inflammatory cytokines in HDPCs treated by EZH2 complex or EZH2 siRNA with or without rhTNF-α were examined by quantitative real-time polymerase chain reaction (q-PCR). The levels of secreted inflammatory cytokines including IL-6, IL-8, IL-15, CCL2 and CXCL12 in culture supernatants were measured by Luminex assay. In rat pulpitis model, the effects of EZH2 on dental pulp tissues were verified by histology. We invested the mechanisms of the effect of EZH2 on the inflammatory factors by ChIP assay.
EZH2 down-regulation inhibited the expression of inflammatory factors, including IL-6, IL-8, IL-15, CCL2 and CXCL12 in HDPCs. EZH2 complex promoted the expression and secretion of these inflammatory factors in HDPCs, while EZH2 silencing could attenuate the promotion of inflammatory factors that were induced by rhTNF-α. In pulpitis models of rats, EZH2 down-regulation inhibited the inflammatory process of dental pulp while EZH2 complex showed no significant facilitation of pulpal inflammation. In addition, EZH2 could bind on the promoters of IL-6, IL-8 and CCL2, but not IL-15 and CXCL12, to affect the transcription of these proinflammatory cytokines.
In HDPCs, EZH2 could induce inflammation, while EZH2 down-regulation could attenuate the inflammatory responses. EZH2 plays an important role in this inflammatory process of dental pulp.
牙髓病是一种多因素疾病，可能是由遗传、表观遗传和环境因素之间的复杂相互作用引起的。本研究旨在评估增强子结合因子 2（EZH2）在人牙髓细胞（HDPCs）和牙髓组织炎症反应中的作用。
通过实时定量聚合酶链反应（q-PCR）检测 EZH2 复合物或 EZH2 siRNA 处理后 HDPCs 中炎症细胞因子的表达，以及 rhTNF-α作用下 EZH2 对 HDPCs 分泌的炎症细胞因子（包括 IL-6、IL-8、IL-15、CCL2 和 CXCL12）的影响。在大鼠牙髓炎模型中，通过组织学验证 EZH2 对牙髓组织的影响。通过 ChIP assay 研究 EZH2 对炎症因子的作用机制。
EZH2 下调抑制了 HDPCs 中包括 IL-6、IL-8、IL-15、CCL2 和 CXCL12 在内的炎症因子的表达。EZH2 复合物促进了 HDPCs 中这些炎症因子的表达和分泌，而 EZH2 沉默可减弱 rhTNF-α诱导的炎症因子的促进作用。在大鼠牙髓炎模型中，EZH2 下调抑制了牙髓的炎症过程，而 EZH2 复合物对牙髓炎症没有明显的促进作用。此外，EZH2 可与 IL-6、IL-8 和 CCL2 的启动子结合，而不与 IL-15 和 CXCL12 结合，从而影响这些促炎细胞因子的转录。
在 HDPCs 中，EZH2 可诱导炎症，而 EZH2 下调可减弱炎症反应。EZH2 在牙髓的炎症过程中发挥重要作用。
