Cross-Sectional Analysis of Matrix Metalloproteinases and Bone Resorption Regulators in Apical Periodontitis: Linking Molecular Mechanisms with Clinical and Histopathological Features.

Abstract

<h4>Objectives</h4>(a) To quantify the relative gene expression of matrix metalloproteinases (MMP) <i>-2</i>, <i>-9</i>, their tissue inhibitor (TIMP) <i>-2</i>, receptor activator of nuclear factor kappa-B ligand <i>(RANKL)</i>, and osteoprotegerin <i>(OPG)</i> in human apical periodontitis (AP) and to associate it with levels of these molecules in healthy dental pulps. (b) To assess differences in gene expression among AP lesions stratified by clinical, radiographic, and histopathological features. (c) Finally, a potential correlation of investigated molecules was explored in AP samples.<h4>Materials and methods</h4>The study cohort comprised 80 AP lesions obtained from 80 adult volunteers during apicoectomy procedures. The healthy control cohort consisted of 50 dental pulp samples from intact teeth extracted for orthodontic purposes, collected from 50 voluntary donors. Relative gene expression of <i>MMP-2, MMP-9, TIMP-2, RANKL,</i> and <i>OPG</i> was assessed in all tissue samples using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). Statistical analyses included the Chi-square test, Student's t-test, Mann-Whitney U test, and Spearman correlation.<h4>Results</h4>Higher gene expression levels of <i>RANKL, OPG, MMP-2,</i> and <i>MMP-9</i> were observed in the study compared to the healthy cohort (p=0.048, p=0.002, p=0.048, and p=0.012, respectively). Higher relative expression of the <i>MMP2</i> gene was observed in smaller lesions compared to large lesions (p=0.021). Significant positive correlations were observed between the investigated mediators.<h4>Conclusions</h4>Concurrent overexpression of the studied mediators, along with their positive correlations in AP lesions, indicates their coordinated role in disease progression and alveolar bone resorption.