Fisetin Attenuates Experimental Periodontal Disease in Rats via Regulating BMP-2/TIMP-1 and OPG/RANKL Signaling Pathways

Abstract

Background: Periodontitis is a persistent inflammatory condition that mainly affects the supportive tissues of the teeth, comprising the gingiva, periodontal ligament, and alveolar bone.Objectives: The present study focused on addressing fisetin’s therapeutic activities against the experimental periodontitis model in rats.Materials and Methods: Experimental periodontitis was initiated in rats by ligation procedure. The fisetin treatment was given with three different dosages for 10 days, and finally, rats were sacrificed on the 11th day, and subsequently, samples were collected for additional assays. The extent of periodontal damage was assessed by quantifying alveolar bone loss (ABL). The inflammatory and osteoblast cell quantities were enumerated on stained tissue slides. The concentrations of oxidative stress biomarkers, bone mineral contents, inflammatory cytokines, glucose, and glycated hemoglobin (HbA) levels in the experimental rats were assessed using commercial kits. The bone morphogenetic protein-2 (BMP-2), matrix metalloproteinase-8 (MMP-8), tissue inhibitor of metalloproteinase-1 (TIMP-1), receptor activator of nuclear factor kappa-Β ligand (RANKL), and osteoprotegerin (OPG) concentrations were assessed using commercially procured kits.Results: The results of this study demonstrated that fisetin treatment successfully reduced ABL, osteoclast, and inflammatory cell counts and increased osteoblast cell numbers in the rats with periodontitis. The levels of glucose and HbA1c were reduced, and bone mineral levels were elevated by fisetin in periodontitis-induced rats. The contents of oxidative stress biomarkers, inflammatory cytokines, inducible nitric oxide synthase, and MMP-8 were effectively reduced in the fisetin-treated rats with periodontitis. Furthermore, the fisetin treatment successfully ameliorated the pathological changes induced by periodontitis in rats by regulating BMP-2/TIMP-1 and OPG/RANKL expressions.Conclusion: These results highlight that fisetin treatment successfully reduced ABL and promoted periodontal tissue regeneration in rats with experimental periodontitis. Therefore, it can be a talented salutary candidate to treat periodontal diseases in the future.

Keywords: Alveolar bone; fisetin; OPG/RANKL pathway; osteoblasts; periodontal disease