PPARa Modulation of Macrophage Polarization and Inflammatory Signaling in Periodontitis 9008

Abstract Description Periodontitis (PD), a leading cause of tooth and jawbone loss, is increasingly recognized as a contributor to systemic diseases, potentially mediated by inflammatory signals from the periodontal microbiome. Macrophages, through their polarization into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, play a critical role in PD pathogenesis. Dysregulated macrophage activity exacerbates both local and systemic inflammation, highlighting the need for targeted therapeutic strategies. Peroxisome Proliferator-Activated Receptors (PPARs), particularly PPARα, have emerged as key regulators of inflammation. Traditionally used in lipid metabolism disorders, PPAR agonists have demonstrated anti-inflammatory properties in chronic inflammatory diseases. Our research identifies significant downregulation of PPARα in Porphyromonas gingivalis (Pg)-induced PD models, with PPARα activation shown to alleviate inflammation and prevent bone loss by modulating macrophage polarization. PPARα agonists inhibit NF-?B signaling, reducing M1 polarization, while enhancing M2 markers associated with tissue repair and inflammation resolution. Moreover, PPARα influences the β-catenin-TCF-4 pathway, further regulating macrophage activity. These findings establish PPARα as a key player in macrophage modulation and underscore its therapeutic potential in PD. By targeting macrophage polarization via PPARα activation, this study offers a novel therapeutic approach for PD and related systemic conditions. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)