miR-141-3p Regulates EZH2 to Attenuate Porphyromonas gingivalis Lipopolysaccharide-Caused Inflammation and Inhibition of Osteogenic Differentiation in Human Periodontal Ligament Stem Cells.

Objective: miR-141-3p has been demonstrated to be both anti-inflammatory and osteoprotective. This study is aimed at investigating the effect of miR-141-3p on osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) stimulated by Porphyromonas gingivalis lipopolysaccharide (PgLPS) and its mechanism. Methods: PgLPS was used to induce an inflammatory environment, and overexpression of miR-141-3p was done to assess its effect on hPDLSCs in an inflammatory environment. The level of miR-141-3p and EZH2 in hPDLSCs from each treatment group was detected via qRT-PCR, and the inflammatory factors IL-6 and IL-8 in the supernatant of each group were detected by ELISA. ALP staining and alizarin red staining were used to assess the effect of miR-141-3p on the osteogenic differentiation ability of hPDLSCs, and also, western blot was used to detect expression of osteogenic differentiation-related proteins. Further, dual-luciferase reporter assay examined whether miR-141-3p targeted EZH2. Results: PgLPS led to a significant decrease of miR-141-3p in hPDLSCs. Overexpression of miR-141-3p could enhance ALP activity and alizarin red staining intensity and increase Runx2, OPN and OCN protein expression levels in PgLPS-treated hPDLSCs. Additionally, miR-141-3p could reduce IL-6 and IL-8. miR-141-3p could target and negatively regulate EZH2, and overexpression of EZH2 reversed the promoting effect of miR-141-3p on osteogenic differentiation. Conclusion: miR-141-3p can attenuate PgLPS-induced inhibition of osteogenic differentiation and inflammation in hPDLSCs by negatively regulating EZH2.