Abstract
BackgroundTooth 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.MethodsBone 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.ResultsWe 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.ConclusionsTooth 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.
Highlights
Tooth impaction is a common problem in orthodontic practice and in some cases accompanied by pain and pathological changes of surrounding teeth
Assessment of the Receptor activator of NF-κB ligand (RANKL)/Receptor activator of NFκB (RANK)/OPG axis and a ratio between its components in bone tissue of patients As the RANKL/RANK/OPG signaling axis regulates the interplay between osteoclasts and osteoblasts that can influence bone remodeling [6], we first determined the content of the RANKL/RANK/OPG system components in the bone tissue of patients with tooth impaction
It was shown a slight tendency to decreased content of osteoprotegerin in the bone tissue near the healthy tooth in patients with tooth impaction compared with the control (Fig. 1c, Tukey’s test, p-value 0.048) and we observed a significant decrease in the RANKL content (Fig. 2c, d)
Summary
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). Tooth impaction is generally asymptomatic, and, in most cases, it is recognized by a chance in a routine dental examination, patients seek treatment later than optimal. In some cases, tooth impaction is accompanied by pain, pathological resorption of the surrounding teeth, and even an increased risk of malignancies [1]. Delayed or failed tooth eruption is a common problem in daily orthodontic practice; it is important to understand the cellular and molecular mechanisms underlying blocking tooth from breaking through the gum, to find the most effective orthodontic treatment for patients with IT. The presence of unerupted teeth requires a thorough diagnostics and a balanced approach to the choice of treatment method, which depends on the overall clinical situation, the patient’s age, and general somatic status
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