Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland).
Med Sci Monit. 2018 Sep 21;24:6656-6665. doi: 10.12659/MSM.909093.
BACKGROUND Let-7c-5p is down-regulated in dental pulp tissues in inflammatory disorders. The microRNA (miR) molecule shows an anti-inflammation potential due to its direct regulation of dentin matrix protein-1 (DMP1), which promotes inflammation changes in dental pulp tissues. In the present study, the effect of let-7c-5p on lipopolysaccharide (LPS)-induced pulpitis was detected and the associated mechanism was explored. MATERIAL AND METHODS Dental pulp stem cells (DPSCs) were isolated from rat dental tissues, infected with let-7c-5p lentivirus particles, and subjected to LPS administration to induce inflammation. Then, the effect of let-7c-5p overexpression on LPS-induced impairments on DPSCs were detected and the mechanism was explained by focusing on the DMP1 expression and NF-κB pathway. The role of DMP1 in the anti-inflammation effect of let-7c-5p was assessed by incubating let-7c-5p-expressed DPSCs with DMP1 protein. The results of in vitro assays were verified in LPS-induced rat pulpitis models. RESULTS LPS administration increased the production of IL-1β and TNF-α and decreased DPSCs viability by increasing the expression of DMP1 and activating NF-κB pathway. However, the induced expression of let-7c-5p relieved DPSCs from LPS-induced inflammation and suppressed DMP1 as well as NF-κB pathway. The incubation of let-7c-5p-expressed DPSCs with DMP1 protein blocked the effect of let-7c-5p. In in vivo experiments, the injection of let-7c-5p attenuated LPS-induced pulpitis by inhibiting DMP1-mediated NF-κB pathway. CONCLUSIONS Findings outlined in the current study demonstrated the dental pulp protecting function of let-7c-5p during LPS-induced inflammation, which was exerted by inhibiting the DMP1-mediated NF-κB pathway.
Let-7c-5p 在炎症性疾病的牙髓组织中下调。由于其对牙本质基质蛋白 1(DMP1)的直接调节,miRNA 分子显示出抗炎潜力,促进牙髓组织的炎症变化。在本研究中,检测了 let-7c-5p 对脂多糖(LPS)诱导的牙髓炎的影响,并探讨了相关机制。
从大鼠牙髓组织中分离牙髓干细胞(DPSCs),感染 let-7c-5p 慢病毒颗粒,并用 LPS 处理以诱导炎症。然后,通过关注 DMP1 表达和 NF-κB 通路,检测 let-7c-5p 过表达对 LPS 诱导的 DPSCs 损伤的影响,并解释其机制。通过用 DMP1 蛋白孵育表达 let-7c-5p 的 DPSCs,评估 DMP1 在 let-7c-5p 抗炎作用中的作用。体外实验结果在 LPS 诱导的大鼠牙髓炎模型中得到验证。
LPS 处理通过增加 DMP1 的表达和激活 NF-κB 通路,增加 IL-1β 和 TNF-α 的产生并降低 DPSCs 的活力。然而,诱导的 let-7c-5p 表达减轻了 LPS 诱导的 DPSCs 炎症,并抑制了 DMP1 和 NF-κB 通路。用 DMP1 蛋白孵育表达 let-7c-5p 的 DPSCs 阻断了 let-7c-5p 的作用。在体内实验中,let-7c-5p 的注射通过抑制 DMP1 介导的 NF-κB 通路来减轻 LPS 诱导的牙髓炎。
本研究结果表明,let-7c-5p 在 LPS 诱导的炎症中具有保护牙髓的功能,这是通过抑制 DMP1 介导的 NF-κB 通路实现的。