The Effect of SIRT1 Overexpression on OPG/RANKL Signaling Pathway: Inhibiting Osteoclastogenesis and Periodontitis Progression

Abstract

Background: Periodontitis is a chronic infectious disease that leads to decreased quality of life. However, the relationship between sirtuin 1 (SIRT1) and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) in periodontitis has not been studied. Objective: To elucidate the effects of SIRT1 on OPG/RANKL signaling pathway and periodontitis progression. Methods: In vivo periodontitis models were constructed using 12 male Wistar rats through ligation methods. Gingival fibroblasts were obtained from rat gingival tissues and treated with 1 μg/mL lipopolysaccharide (LPS) for 24 h to induce in vitro periodontitis models. Cell transfection was performed, using plasmid pcDNA3.1 containing the coding sequence of OPG or SIRT1 and Lipofectamine 3000. Hematoxylin and eosin (H&E) kit was used for evaluating histology and tartrate-resistant acid phosphatase (TRAP) staining was implemented for determining the content of osteoclasts. Enzyme linked immunosorbent assay (ELISA) assay was used to detect inflammatory cytokines including interleukin (IL)-1β and tumor necrosis factor (TNF)-α. RT-qPCR (real-time quantitative polymerase chain reaction) was utilized for relative mRNA (messenger ribonucleic acid) levels monitoring. Results: The expression of RANKL was upregulated, while SIRT1 and OPG were downregulated in rat periodontitis models. Moreover, overexpression of OPG attenuated periodontitis progression in vitro. Further studies showed that overexpression of SIRT1 significantly enhanced OPG/RANKL ratio, inhibited osteoclastogenesis and alleviated periodontitis progression. Conclusions: Overexpression of SIRT1 activated OPG/RANKL signaling pathway, inhibited osteoclastogenesis and attenuated periodontitis progression.