Systemic RVX ‐208 Attenuates Experimental Periodontitis Through Inflammatory Host Modulation

ABSTRACT Aims This study investigated whether systemic treatment of RVX‐208, a selective BET protein inhibitor, could ameliorate experimental periodontitis in a prophylactic setting and examined transcriptomic changes associated with RVX‐208 in vitro. Methods Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) was injected into gingiva in mice twice a week for 6 weeks to induce periodontitis. RVX‐208 or vehicle was administered via oral gavage every Monday–Friday, beginning 1 week before LPS injection and continuing for 7 weeks. The periodontal bone loss and osteoclastic activity were evaluated through micro‐CT and histological analyses. THP‐1 human monocytic cells were treated with Pg bacteria, with or without RVX‐208 and JQ1, and RNA‐sequencing was performed. Results Pg LPS delivery led to periodontal bone loss in mice. Compared with vehicle, systemic treatment of RVX‐208 reduced alveolar bone loss and the number of tartrate‐resistant acid phosphatase (TRAP) positive cells. In vitro, RVX‐208 suppressed the expression of a set of inflammatory genes in THP‐1 cells and led to a more moderate and limited effect on transcriptome compared to pan‐BET inhibitor JQ1. Conclusion Systemic RVX‐208 treatment reduced periodontal bone loss in a prophylactic setting in this experimental periodontitis model. In THP‐1 cells, RVX‐208 suppresses the global inflammatory response induced by Pg.