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MicroRNA let-7c-5p Suppressed Lipopolysaccharide-Induced Dental Pulp Inflammation by Inhibiting Dentin Matrix Protein-1-Mediated Nuclear Factor kappa B (NF-κB) Pathway In Vitro and In Vivo

Hao Yuan, Hong Zhang, Lihua Hong, Hongyan Zhao, Jiafeng Wang, He Li, Hongze Che, Zhimin Zhang

(Department of Endodontics, School of Stomatology, Jilin University, Changchun, Jilin, China (mainland))

Med Sci Monit 2018; 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.

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