Immune-Inflammatory Cell Profile and Receptor Activator of Nuclear Factor Kappa B Ligand/Osteoprotegerin Expression in Persistent Apical Periodontitis after Root Canal Retreatment Failure

Abstract

Introduction: This study assessed the immune-inflammatory profile and the expression of bone resorption activators receptor activator of nuclear factor kappa B ligand (RANKL) and inhibitor osteoprotegerin (OPG) in apical periodontitis (n = 20) that persisted after root canal retreatment.

Methods: Immunohistochemistry was used to characterize lymphocyte populations (CD3+, CD45RO+, CD8+, and FoxP3+ cells), macrophages (CD68+), RANKL+ and OPG+ cells in persistent apical periodontitis (PAP) and primary periapical lesions (PPLs). By using quantitative real-time polymerase chain reaction, the mRNA expression of RANKL and OPG in PAP and periodontal ligament from healthy teeth was comparatively analyzed. The data were analyzed by Mann-Whitney, Pearson χ2, and Wilcoxon tests (5% level).

Results: PAP showed an elevated number of FoxP3+ cells compared with PPL (P < .001). The number of CD68+ cells was reduced in the PAP samples compared with the PPLs (P < .001). Similar number of other lymphocyte populations was observed in PAP and PPLs (P > .05 for all comparisons). No differences in the RANKL, OPG, and immune-inflammatory cells were demonstrated when comparing PAP microscopically classified as cyst with those classified as granulomas (P > .05 for all comparisons). The assessment of mRNA expression revealed higher levels of RANKL and OPG in PAP compared with the periodontal ligament from healthy teeth (control) samples (P < .001). Also, a greater expression of RANKL in comparison with OPG was observed in PAP (P < .001).

Conclusions: These findings indicate that PAP consists of biologically active lesions that demonstrate potential of bone resorption (higher expression of RANKL) and is characterized by an immune-inflammatory cell profile that suggests a suppressive and regulatory environment (higher number of FoxP3+ cells and lower number of macrophages) favorable to more chronic clinical behavior.

Keywords: Apical periodontitis; RANK ligand; bone resorption; immunological cells; osteoprotegerin.