Notch Signaling Pathway in Apical Periodontitis: Correlation with Bone Resorption Regulators and Proinflammatory Cytokines

Introduction: The exact mechanisms of periapical bone resorption have not been fully elucidated. This study aimed to analyze the expression of Notch signaling molecules (Notch2, Jagged1, and Hey1) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin [IL]-1 beta, and IL-6) in human apical periodontitis lesions with different receptor activator of nuclear factor kappa B ligand (RANKL)/osteo-protegerin (OPG) ratios and determine their potential correlation. Methods: The study group consisted of 50 periapical lesions collected in conjunction with apicoectomy. The relative gene expression of the investigated molecules (Notch2, Jagged1, Hey1, RANKL, OPG, TNF-alpha, IL-1 beta, and IL-6) in all tissue samples was analyzed using reverse transcriptase real-time polymerase chain reaction. The Student t test, Mann-Whitney U test and Spearman correlation were used for statistical analysis. Results: Based on the RANKUOPG ratio, periapical lesions were either RANKL predominant (RANKL > OPG, n = 33) or OPG predominant (RANKL < OPG, n = 17). Symptomatic lesions occurred more frequently in RANKL-predominant compared with OPG-predominant lesions (24 vs 7, P=.029). Notch2,Jagged1, Hey1, and TNF-alpha were significantly overexpressed in lesions with predominant RANKL compared with lesions with predominant OPG (P =.001, P =.001, P =.027, and P =.016, respectively). Significant correlations were observed between the investigated genes in periapical lesions. Conclusions: Notch signaling appeared to be activated in periapical inflammation. An increase in Notch2, Jagged1, Hey1, and TNF-alpha expression in RANKL-predominant periapical lesions corroborates their joined involvement in extensive periapical bone resorption.