MicroRNAs (miRNAs) are short, noncoding RNAs involved in the regulation of several processes associated with inflammatory diseases and infection. Bacterial infection modulates miRNA expression to subvert any innate immune response. In this study we analyzed, using microarray analysis, the bacterial modulation of miRNAs in bone marrow-derived macrophages (BMMs) in which activity was induced by infection with Porphyromonas gingivalis. The expression of several miRNAs was modulated 3 h postinfection (at a multiplicity of infection of 25). A bioinformatic analysis was performed to further identify pathways related to the innate immune host response under the influence of selected miRNAs. To assess the effects of the miRNAs identified on cytokine secretion (tumor necrosis factor alpha [TNF-␣] and interleukin-10 [IL-10]), BMMs were transfected with selected miRNA mimics and inhibitors. Transfection with mmu-miR-155 and mmumiR-2137 did not modify TNF-␣ secretion, while their inhibitors increased it. Inhibitors of mmu-miR-2137 and mmu-miR-7674 increased the secretion of the anti-inflammatory factor IL-10. In P. gingivalis-infected BMMs, mmu-miR-155-5p significantly decreased TNF-␣ secretion while inhibitor of mmu-miR-2137 increased IL-10 secretion. In vivo, in a mouse model of P. gingivalis-induced calvarial bone resorption, injection of mmu-miR-155-5p or anti-mmu-miR-2137 reduced the size of the lesion significantly. Furthermore, anti-mmu-miR-2137 significantly reduced inflammatory cell infiltration, osteoclast activity, and bone loss. Bioinformatic analysis demonstrated that pathways related to cytokine-and chemokinerelated pathways but also osteoclast differentiation may be involved in the effects observed. This study contributes further to our understanding of P. gingivalis-induced modulation of miRNAs and their physiological effects. It highlights the potential therapeutic merits of targeting mmu-miR-155-5p and mmumiR-2137 to control inflammation induced by P. gingivalis infection.
Aim
The aim of this study was to evaluate the effect of Kava-241, an optimized Piper methysticum Kava compound, on periodontal destruction in a collagen antibody primed oral gavage model of periodontitis.
Methods
Experimental periodontitis was induced by oral gavage of Porphyromonas gingivalis (P.gingivalis) + type-II collagen antibody (AB) in mice during 15 days. Mice were treated with Kava-241 concomitantly or prior to P.gingivalis gavage and compared to untreated mice. Comprehensive histomorphometric analyses were performed.
Results
Oral gavage with P.gingivalis induced mild epithelial downgrowth and alveolar bone loss while oral gavage with additional AB priming had greater tissular destruction in comparison to gavage alone (p<0.05). Kava-241 treatment significantly (p<0.05) reduced epithelial downgrowth (72%) and alveolar bone loss (36%) in P.gingivalis+AB group. This Kava-241 effect was associated to a reduction of inflammatory cells counts within soft tissues and an increase of fibroblasts (p<0.05).
Conclusion
Priming with type-II collagen antibody with oral gavage is a fast and reproducible model of periodontal destruction adequate for the evaluation of novel therapeutics. The effect of Kava-241 shows promise in the prevention and treatment of inflammation and alveolar bone loss associated with periodontitis. Further experiments are required to determine molecular pathways targeted by this therapeutic agent.
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