Department of Pediatric Dentistry, Central Laboratory, Peking University School and Hospital of Stomatology & National Center of Stomatology &National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR, China.
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China.
Inflammation. 2021 Oct;44(5):1927-1936. doi: 10.1007/s10753-021-01470-7. Epub 2021 Apr 21.
Pulpitis is a complicated chronic inflammatory process which can be in a dynamic balance between damage and repair. The extracellular matrix plays an important regulatory role in wound healing and tissue repair. The aim of this study was to explore the role of the epigenetic mark, enhancer of zeste homolog 2 (EZH2) on the degradation of extracellular matrix during pulpitis. Quantitative polymerase chain reaction was used to assess the expression of matrix metalloproteinases (MMPs) and type I collagen in human dental pulp cells (HDPCs) upon EZH2 and EI1 (EZH2 inhibitor) stimulation. The mechanism of EZH2 affecting extracellular matrix was explored through quantitative polymerase chain reaction and Western blot. A rat model of dental pulp inflammation was established, and the expression of type I collagen in dental pulp under EZH2 stimulation was detected by immunohistochemical staining. EZH2 upregulated the expression of MMP-1, MMP-3, MMP-8, and MMP-10 and decreased the production of type I collagen in HDPCs, while EI1 had the opposite effect. EZH2 activated the nuclear factor-kappa B (NF-κB) and p38 signaling pathways in HDPCs, the inhibition of which reversed the induction of MMPs and the suppression of type I collagen. EZH2 can downregulate the type I collagen levels in an experimental model of dental pulpitis in rats. EZH2 promotes extracellular matrix degradation via nuclear factor-κB (NF-κB) and P38 signaling pathways in pulpitis. EZH2 can decrease the type I collagen levels in vivo and in vitro.
牙髓炎症是一种复杂的慢性炎症过程，可以在损伤和修复之间达到动态平衡。细胞外基质在伤口愈合和组织修复中起着重要的调节作用。本研究旨在探讨表观遗传标记增强子结合蛋白 2（EZH2）在牙髓炎症过程中外基质降解中的作用。采用定量聚合酶链反应检测 EZH2 和 EI1（EZH2 抑制剂）刺激下人牙髓细胞（HDPCs）中基质金属蛋白酶（MMPs）和 I 型胶原的表达。通过定量聚合酶链反应和 Western blot 探讨 EZH2 影响细胞外基质的机制。建立大鼠牙髓炎症模型，通过免疫组织化学染色检测 EZH2 刺激下牙髓中 I 型胶原的表达。EZH2 上调 MMP-1、MMP-3、MMP-8 和 MMP-10 的表达，降低 HDPCs 中 I 型胶原的产生，而 EI1 则有相反的作用。EZH2 在 HDPCs 中激活核因子-κB（NF-κB）和 p38 信号通路，抑制该通路可逆转 MMPs 的诱导和 I 型胶原的抑制。EZH2 可下调大鼠牙髓炎症实验模型中 I 型胶原的水平。EZH2 通过核因子-κB（NF-κB）和 P38 信号通路促进牙髓炎中外基质的降解。EZH2 可降低体内和体外 I 型胶原的水平。
