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 study aimed to evaluate 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, that was taken near the healthy tooth in patients with tooth impaction; 3 – bone tissue, that was collected 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 using ANOVA followed by Tukey’s post-hoc test. P-value ≤0.05 was 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 (1.46-, 1.48-, and 1.42-fold respectively), reflecting the 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 folds 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 folds). 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.

Rosehip Extract-Functionalized Magnesium Hydroxide Nanoparticles and Its Effect on Osteoblastic and Osteoclastic Cells

“…Comparing the two NPs, Mg(OH) 2 RH induced the genes coding for the early and late transcription factors, respectively, Runx2 and Osterix, collagen type I, the main component of the bone extracellular matrix, and ALP, the enzyme needed for the initiation of the matrix mineralization [ 52 ]. Expression of OPG, a regulatory inhibitor of osteoclastogenesis in the osteoblast-osteoclast RANKL/RANK/OPG signaling [ 53 ] appeared to not be affected, suggesting that the interaction between the two cell types is probably not significantly affected. Several factors might account for the higher osteoblastic inductive effect of Mg(OH) 2 RH NPs.…”

Evaluation of Vitamin D (25OHD), Bone Alkaline Phosphatase (BALP), Serum Calcium, Serum Phosphorus, Ionized Calcium in Patients with Mandibular Third Molar Impaction. An Observational Study

“…The eruption phenomenon requires the participation of osteoclasts that intervene in the process of reabsorption of the alveolar bone, mainly mediated by the expression of the colony-stimulating factor 1 (CSF-1), of the RANK, the RANK ligand (RANKL) and of the osteoprotegerin (OPG). The RANKL/RANK/OPG system is considered the path that modulates bone remodeling and can control the dental rash [73][74][75].…”

The Pathophysiology of Osteoporosis after Spinal Cord Injury

“…Some therapies target the RANKL/RANK/OPG pathway. Denosumab, a monoclonal antibody against human RANKL, inhibits binding and activation of RANK, inhibiting RANK-mediated osteoclastogenesis [ 125 , 166 ]. Although effective in limiting bone loss, competitive RANKL inhibition may have off target effects on immune function [ 167 ].…”