Inhibitory effect of roflumilast on experimental periodontitis.

BACKGROUND: Phosphodiesterase-4 (PDE4) has been identified as a valid therapeutic target in several inflammatory diseases. In this study, we assessed PDE4 in gingival tissue from patients with chronic periodontitis and evaluated the therapeutic effects of the PDE4 inhibitor, roflumilast, in an experimental rat model of periodontitis. METHODS: Gingival tissue specimens from 20 healthy subjects and 20 patients with periodontitis were collected, and the mRNA expression levels of PDE4, interleukin (IL)-1beta, and IL-6 were assessed. Ninety rats were divided randomly into three groups (30 per group): non-ligature group, ligature-induced periodontitis group (L), and ligature-induced periodontitis with roflumilast administered group (5 mg/kg/d) (L+R). Rats were euthanized on days 3, 8, and 14. Alveolar bone resorption was analyzed using microcomputed tomography. Inflammation and osteoclast number were analyzed histologically. Finally, the mRNA expression levels of PDE-4, IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and nuclear factor kappa B (NF-kappaB) were assessed in the rat gingival tissue. RESULTS: The mRNA expression levels of PDE4, IL-1beta, and IL-6 in the gingiva were significantly higher in patients with periodontitis compared with healthy individuals (P <0.05). Alveolar bone loss, degree of inflammation, number of TRAP-positive multinucleated osteoclasts, and mRNA expression levels of IL-1beta, IL-6, TNF-alpha, NF-kappaB, and PDE4 in the L+R group were significantly lower than those in the L group (P <0.05). CONCLUSIONS: PDE4 expression was increased in the gingiva of patients with periodontitis. Roflumilast may decrease alveolar bone loss and the expression of inflammatory cytokines in rats with ligature-induced periodontitis.