The regulatory role of the RANKL/RANK/OPG signaling pathway in the mechanisms of tooth eruption in patients with impacted teeth

Abstract

Background: Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective orthodontic treatment for patients with impacted teeth (IT). RANK (receptor activator of NF-κB) / RANKL (RANK ligand) / OPG (osteoprotegerin) signaling pathway controls bone resorption and may be involved in the regulation of tooth eruption. The aim of the study was to evaluate the bone remodeling based on the assessment of the RANKL/RANK/OPG status in patients with IT. Methods: Bone samples from 18 patients (mean age 25.27±3.34) were divided into 3 groups: 1 – bone tissue of healthy persons (control group); 2 – bone tissue taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue taken near the IT. Levels of RANKL, RANK, OPG, osteocalcin (OC), NF-κB p65 subunit, NFATc1 and caspase-3 were determined by Western blotting. The difference between groups was assessed by one-way ANOVA. P-values less than 0.05 were considered statistically significant.Results: We established a 1.73-fold elevation of RANK level in the IT area vs. control, indicating the recruitment of preosteoclasts. An increase in RANKL, OPG and OC content was demonstrated (by 1.46, 1.48, and 1.42 fold respectively), reflecting high activity of osteoblasts near the IT. Despite the activation of the RANKL/RANK/OPG system in the impaction area, NF-κB and NFATc1 levels did not change compared vs. control, indicating a blocked/delayed process of osteoclastogenesis. We found a decrease in the content of procaspase-3 (1.28-fold), while the level of its active form p17 increased by 2.26 fold near the healthy tooth in patients with IT compared with control. In the area of ​​IT we observed an increase in procaspase-3 and p17 levels (1.32 and 1.78 fold). This reflects impairments of caspase-3 activation and accumulation of its inactive form in the IT area that may contribute to the tooth eruption failure.Conclusions: Tooth impaction may be associated with the disturbances in the caspase-3 cascade activation and the imbalance in the RANKL/RANK/OPG system, and as a result, blocked bone resorption.