MicroRNA-200c Attenuates Periodontitis By Modulating Proinflammatory And Osteoclastogenic Mediators
This study tested whether miR-200c can attenuate the inflammation and alveolar bone resorption in periodontitis using an in vitro and a rat model. Polyethylenimine (PEI) was used to facilitate the transfection of plasmid DNA encoding miR-200c into primary human gingival fibroblasts (HGFs) and gingival tissues of rats. We first analyzed how proinflammatory and osteoclastogenic mediators in HGFs with overexpression of miR-200c responded to P. gingivalis lipopolysaccharide (LPS-PG) challenge in vitro. We observed that overexpression of miR-200c significantly reduced interleukin (IL)-6 and 8 and repressed interferon-related developmental regulator-1 (IFRD1) in HGFs. miR-200c also down-regulated p65 and p50. In a rat model of periodontitis induced by LPS injection at the gingival sulcus of the 2nd maxillary molar, we analyzed how the mediators in rat gingiva and alveolar bone resorption responded to miR-200c treatment by local injection of PEI-plasmid miR-200c nanoplexes. We observed that the local injection of miR-200c significantly upregulated miR-200c expression in gingiva and reduced IL-6, IL-8, IFRD1, and the ratio of receptor activator of nuclear factor kappa-Β ligand / osteoprotegerin ((RANKL / OPG). Using µCT analysis and histomorphometry we further confirmed that local treatment with miR-200c effectively protected alveolar bone resorption in the rat model of periodontitis by reducing the distance between the cemento-enamel junction (CEJ) and the alveolar bone crest (ABC) and the interradicular space in the upper maxilla at 2nd maxillary molar. These findings imply that miR-200c may serve as a unique means to prevent periodontitis and associated bone loss.