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.

The authors' abstract, as published at the source. Journal of Periodontal Research, 2026 · DOI ↗