The down-regulation of Notch 1 signaling contributes to the severity of bone loss in aggressive periodontitis

Abstract

Background The exact mechanisms of bone resorption in periodontitis have not been fully elucidated. The aims of this study were to analyze the expression of Notch signaling molecules, bone remodeling mediators, and pro-inflammatory cytokines in periodontitis patients and to determine their potential correlations. Methods The study included 130 individuals: 40 with aggressive periodontitis (AP group), 40 with chronic periodontitis (CP group), and 50 periodontally healthy controls. Total RNA was extracted from gingival crevicular fluid samples and relative gene expression of investigated molecules (Notch 1, Notch 2, Jagged 1, Hes 1, Hey 1, TNF-alpha, IL-17, RANKL, and OPG) was determined by reverse transcriptase - real-time polymerase chain reaction (RT-qPCR). Results In AP group, a significant increase of Notch 2, TNF-alpha, IL-17 and RANKL and a significant decrease of Notch 1 and Jagged 1 expression were observed compared to control group (P = 0.023, P = 0.005, P = 0.030, and P = 0.001 P = 0.031 and P = 0.029, respectively). Notch 2 and RANKL were also overexpressed in CP group compared to controls (P = 0.001 and P = 0.011). Significant correlations were observed in AP group between expression levels of the analyzed genes. Conclusion The present findings implicate Notch 2 overexpression in the ethiopathogenesis of bone resorption in aggressive and chronic periodontitis. The down-regulation of Notch 1 and Jagged 1 and loss of their osteoprotective function might cause a more excessive osteoclast formation and contribute to greater osteolysis in aggressive periodontitis.