MicroRNA-200c Attenuates Periodontitis by Modulating Proinflammatory and Osteoclastogenic Mediators
Adil Akkouch1, Min Zhu1, Miguel Romero-Bustillos2
11Iowa Institute for Oral Health Research, College of Dentistry, The University of Iowa, Iowa City, Iowa.
Abstract:
This study tested whether microRNA (miR)-200c can attenuate the inflammation and alveolar bone resorption in periodontitis by 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 Porphyromonas 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 downregulated p65 and p50. In a rat model of periodontitis induced by an LPS injection at the gingival sulcus of the second maxillary molar (M2), we analyzed how the mediators in rat gingiva and alveolar bone resorption responded to miR-200c treatment by a local injection of PEI-plasmid miR-200 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-B ligand/osteoprotegerin. Using micro-computed tomography 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 and the alveolar bone crest and the inter-radicular space in the upper maxilla at M2. These findings imply that miR-200c may serve as a unique means to prevent periodontitis and associated bone loss.
Insights
MicroRNA-200c reduces inflammation and bone loss in periodontitis. This study shows miR-200c protects against alveolar bone resorption and inflammatory mediators in both cell and animal models.
Area of Science:
- Periodontology
- Molecular Biology
- Biomedical Engineering
Background:
- Periodontitis involves inflammation and alveolar bone resorption.
- MicroRNAs (miRNAs) play roles in regulating inflammatory and bone remodeling processes.
- miR-200c's potential therapeutic role in periodontitis requires investigation.
Purpose of the Study:
- To investigate the therapeutic potential of microRNA (miR)-200c in attenuating inflammation and alveolar bone resorption in periodontitis.
- To evaluate the effects of miR-200c overexpression on inflammatory and osteoclastogenic mediators in human gingival fibroblasts (HGFs) challenged with Porphyromonas gingivalis lipopolysaccharide (LPS-PG).
- To assess the efficacy of local miR-200c delivery in a rat model of periodontitis.
Main Methods:
- In vitro study using primary HGFs transfected with miR-200c using polyethylenimine (PEI).
- In vivo study using a rat model of periodontitis induced by LPS injection.
- Local delivery of miR-200c via PEI-plasmid nanoplexes.
- Analysis of inflammatory mediators (IL-6, IL-8, IFRD1, p65, p50), osteoclastogenic factors (RANKL/OPG ratio), micro-computed tomography, and histomorphometry.
Main Results:
- Overexpression of miR-200c in HGFs reduced IL-6, IL-8, IFRD1, p65, and p50 expression following LPS-PG challenge.
- Local injection of miR-200c in rats significantly upregulated gingival miR-200c expression.
- miR-200c treatment reduced IL-6, IL-8, IFRD1, and the RANKL/OPG ratio, and effectively protected against alveolar bone resorption in the rat model.
Conclusions:
- miR-200c effectively suppresses inflammatory and osteoclastogenic mediators in periodontitis.
- Local delivery of miR-200c demonstrates therapeutic potential in preventing periodontitis-associated alveolar bone loss.
- miR-200c represents a promising therapeutic agent for periodontitis management.
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