Faculty Collaboration Database

Notch Signaling Pathway in Apical Periodontitis: Correlation with Bone Resorption Regulators and Proinflammatory Cytokines. J Endod 2019 Feb;45(2):123-128

Date

12/26/2018

Pubmed ID

30580840

DOI

10.1016/j.joen.2018.10.015

Scopus ID

2-s2.0-85058677966 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

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-α], interleukin [IL]-1β, and IL-6) in human apical periodontitis lesions with different receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (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-α, IL-1β, 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 RANKL/OPG 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-α 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-α expression in RANKL-predominant periapical lesions corroborates their joined involvement in extensive periapical bone resorption.

Author List

Nikolic N, Jakovljevic A, Carkic J, Beljic-Ivanovic K, Miletic M, Soldatovic I, Andric M, Ivanovic V, Milasin J

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Bone Resorption
Cytokines
Female
Gene Expression
Humans
Inflammation Mediators
Male
Middle Aged
Osteoprotegerin
Periapical Periodontitis
RANK Ligand
Receptor, Notch2
Signal Transduction
Young Adult