REV-ERBα Targeting Shows Promise for Treating Periodontitis-Induced Bone Loss

The study investigates the role of circadian rhythm disruption in periodontitis and its contribution to alveolar bone resorption. A novel Periodontitis Circadian Rhythm Score (PeriCRS) model, developed via machine learning using periodontal transcriptomic data, identified key molecular clock genes, particularly NR1D1 (encoding REV-ERBα), as regulators in periodontitis. In mice, circadian rhythm disruption exacerbated alveolar bone loss, and REV-ERBα activation with the agonist SR9009 reduced RANKL-induced osteoclast differentiation. In vivo, SR9009 alleviated bone loss associated with periodontitis. The IL-22-STAT3 pathway was found to inhibit REV-ERBα expression, modulating osteoclastogenesis. These findings suggest REV-ERBα as a potential target for treating periodontitis-related bone resorption.