scholarly journals Vitamin D Auto-/Paracrine System Is Involved in Modulation of Glucocorticoid-Induced Changes in Angiogenesis/Bone Remodeling Coupling

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Olha Lisakovska ◽  
Ihor Shymanskyi ◽  
Dmytro Labudzynskyi ◽  
Anna Mazanova ◽  
Mykola Veliky
Keyword(s):  
Vitamin D ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Maximal Load ◽  
Biomechanical Parameters ◽  
Induced Changes

Osteoporosis is a devastating side effect of chronic glucocorticoid (GC) treatment. Despite the crucial role of vitamin D (VD) in bone homeostasis, the precise molecular mechanisms of its action on GC-induced disturbances of bone remodeling remain undefined. The study was performed to elucidate the relation of VD status to GC-induced changes of the angiogenesis/osteogenesis/bone resorption coupling in bone tissue. Female Wistar rats received prednisolone (5 mg/kg of b.w.) with or without VD3 (1000 IU/kg of b.w., for 30 days). Biomechanical parameters of rat femurs were assessed by the three-point bending test. The levels of calcium, inorganic phosphate, activity of total alkaline phosphatase (ALP), and its isoenzymes were determined spectrophotometrically. Vascular endothelial growth factor-A (VEGF-A) and caspase-3 protein levels were detected by western blotting. Vdr and Cyp27b1 mRNAs were measured by qRT-PCR. Receptor activator of nuclear factor κB (RANK) expression in bone sections was visualized immunohistochemically. Serum 25(OH)D was assayed by ELISA. GC administration led to a decrease in maximal load (by 1.2-fold) and stiffness and toughness (by 1.3-fold), which was accompanied by a 3-fold reduction of 25(OH)D level, an elevation of the ALP bone isoenzyme activity in serum, hypocalcaemia, and hypophosphatemia. Along with prednisolone-induced VD deficiency, an impaired synthesis of Vdr (−30%) and Cyp27b1 (+71%) mRNA was observed, reflecting deregulation of bone tissue VD-auto-/paracrine system. GC caused an increase in caspase-3 content, suppressed the synthesis of the osteoclastic marker RANK, and altered angiogenesis/osteogenesis coupling by significantly reducing the level of VEGF-A.VD3 treatment restored serum 25(OH)D content and the expression of key components of the VD-auto-/paracrine system. VD3 supplementation diminished cell apoptosis and strongly improved angiogenesis/osteogenesis coupling as well as mineral metabolism and biomechanical parameters of femurs in GC-administered rats. Thus, VD3 can have a beneficial effect on the correction of GC-induced pathological changes in bone remodeling.

scholarly journals DON-induced changes in bone homeostasis in mink dams

2017 ◽  
Vol 61 (3) ◽  
pp. 357-362 ◽  
Author(s):  
Ewa Tomaszewska ◽  
Piotr Dobrowolski ◽  
Siemowit Muszyński ◽  
Krzysztof Kostro ◽  
Iwona Taszkun ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Bone Mineral ◽  
Wall Thickness ◽  
Vertical Wall ◽  
Control Group ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Cross Sectional ◽  
Final Body Weight ◽  
Induced Changes

AbstractIntroduction: The aim of the study was to investigate the mechanical and geometric properties as well as bone tissue and mineral density of long bones in mink dams exposed to deoxynivalenol (DON) since one day after mating, throughout gestation (ca. 46 d) and lactation to pelt harvesting. Material and Methods: Thirty clinically healthy multiparous minks (Neovison vison) of the standard dark brown type were used. After the mating, the minks were randomly assigned into two equal groups: nontreated control group and DON group fed wheat contaminated naturally with DON at a concentration of 1.1 mg·kg-1of feed. Results: The final body weight and weight and length of the femur did not differ between the groups. However, DON contamination decreased mechanical endurance of the femur. Furthermore, DON reduced the mean relative wall thickness and vertical wall thickness of the femur, while vertical cortical index, midshaft volume, and cross-sectional moment of inertia increased. Finally, DON contamination did not alter bone tissue density, bone mineral density, or bone mineral content, but decreased the values of all investigated structural and material properties. Conclusion: DON at applied concentration probably intensified the process of endosteal resorption, which was the main reason for bone wall thinning and the weakening of the whole bone.

scholarly journals The Molecular Mechanisms by Which Vitamin D Prevents Insulin Resistance and Associated Disorders

2020 ◽  
Vol 21 (18) ◽  
pp. 6644 ◽  
Author(s):  
Izabela Szymczak-Pajor ◽  
Józef Drzewoski ◽  
Agnieszka Śliwińska
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Review Article ◽  
Bone Homeostasis ◽  
Glucose And Lipid Metabolism ◽  
The University ◽  
Chronic Hyperglycaemia

Numerous studies have shown that vitamin D deficiency is very common in modern societies and is perceived as an important risk factor in the development of insulin resistance and related diseases such as obesity and type 2 diabetes (T2DM). While it is generally accepted that vitamin D is a regulator of bone homeostasis, its ability to counteract insulin resistance is subject to debate. The goal of this communication is to review the molecular mechanism by which vitamin D reduces insulin resistance and related complications. The university library, PUBMED, and Google Scholar were searched to find relevant studies to be summarized in this review article. Insulin resistance is accompanied by chronic hyperglycaemia and inflammation. Recent studies have shown that vitamin D exhibits indirect antioxidative properties and participates in the maintenance of normal resting ROS level. Appealingly, vitamin D reduces inflammation and regulates Ca2+ level in many cell types. Therefore, the beneficial actions of vitamin D include diminished insulin resistance which is observed as an improvement of glucose and lipid metabolism in insulin-sensitive tissues.

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

2020 ◽  
Author(s):  
Ludmila Brodetska ◽  
Larysa Natrus ◽  
Olha Lisakovska ◽  
Olexandr Kaniura ◽  
Liudmyla Iakovenko ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Tissue ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Active Form ◽  
Tooth Eruption ◽  
Control Group ◽  
Impacted Teeth ◽  
Tooth Impaction

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.

scholarly journals Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Rinaldo Florencio-Silva ◽  
Gisela Rodrigues da Silva Sasso ◽  
Estela Sasso-Cerri ◽  
Manuel Jesus Simões ◽  
Paulo Sérgio Cerri
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Current Data ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Bone Biology ◽  
Structure And Functions

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

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

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ludmila Brodetska ◽  
Larysa Natrus ◽  
Olha Lisakovska ◽  
Olexandr Kaniura ◽  
Liudmyla Iakovenko ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Tissue ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Active Form ◽  
Tooth Eruption ◽  
Control Group ◽  
Impacted Teeth ◽  
Tooth Impaction

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.

scholarly journals Combined Extracts of Herba Epimedii and Fructus Ligustri Lucidi Rebalance Bone Remodeling in Ovariectomized Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Yuheng Chen ◽  
Xiaoxi Li ◽  
Xiufeng Tang ◽  
Yingying Gao ◽  
Ping Yu ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Molecular Mechanisms ◽  
Ovariectomized Rats ◽  
Tartrate Resistant Acid Phosphatase ◽  
Protective Effects ◽  
Mineral Density ◽  
Fructus Ligustri Lucidi ◽  
Maximal Load ◽  
Ovx Rats ◽  
Herba Epimedii

This study aimed to investigate the osteoprotective effect and the possible molecular mechanisms of the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi on postmenopausal osteoporosis (PMOP). Forty-eight female SD rats were sham-operated (Sham, n = 8) or ovariectomized (OVX, n = 40). Then after a week, OVX rats were divided randomly into five groups (n = 8 in each group): OVX, extracts of Herba Epimedii (HE, 0.35 g/kg), extracts of Fructus Ligustri Lucidi (FLL, 0.35 g/kg), combined extracts of HE and FLL (HE & FLL, 0.20 g/kg HE plus 0.15 g/kg FLL), and Raloxifene hydrochloride (RH, 6.25 mg/kg) groups. All groups were administered once daily for 12 weeks. Indicators related to bone remodeling were detected, including estradiol (E2), bone mineral density (BMD), maximal load, ultimate deflection, micro-CT properties, tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) levels in serum and bone, and the protein and mRNA expression of bone turnover markers (RANKL, M-CSF, Wnt5a, Atp6v0d2, OPG, IGF-1, TGF-β1, and Bmp-2). Results showed that the combined extracts could increase serum E2 levels and BMD, enhance bone strength, reserve bone microstructure degeneration, promote bone formation, and inhibit bone resorption through upregulating the mRNA and protein expression of OPG, IGF-1, TGF-β1, and Bmp-2, while downregulating RANKL, M-CSF, Wnt5a, and Atp6v0d2. These findings demonstrated that the combined extracts of Herba Epimedii and Fructus Ligustri Lucidi with bone protective effects on OVX rats might be an alternative medicine for the treatment of PMOP.

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

2019 ◽  
Author(s):  
Petro Flis ◽  
Ludmila Brodetska ◽  
Olexandr Kaniura ◽  
Olha Lisakovska ◽  
Larysa Natrus ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Tissue ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Active Form ◽  
Tooth Eruption ◽  
Control Group ◽  
Impacted Teeth ◽  
Tooth Impaction

Abstract Background Tooth impaction is a common problem in orthodontic practice and usually accompanied by pain and pathological changes of surrounding teeth. Understanding the cellular and molecular mechanisms underlying tooth impaction allows finding the most effective way of orthodontic treatment for patients with impacted teeth (IT). The 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 20 patients (mean age 15.27, SD = 3.83) 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 p65subunit, 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.

Parathyroid Hormone in the Regulation of Bone Growth and Resorption in Health and Disease

2021 ◽  
Vol 76 (5) ◽  
pp. 506-517
Author(s):  
Maria V. Vorontsova ◽  
Konstantin Y. Kulebyakin ◽  
Nadezhda V. Makazan ◽  
Leila S. Sozaeva ◽  
Pyotr A. Tyurin-Kuzmin
Keyword(s):  
Parathyroid Hormone ◽  
Bone Tissue ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Bone Growth ◽  
The Body ◽  
Signaling Cascades ◽  
Main Body ◽  
Bone Homeostasis ◽  
Cellular Mechanisms

Parathyroid hormone (PTH) is a key hormone responsible for regulation of calcium homeostasis in the body. Since the main body calcium depot is bone tissue, PTH has a decisive effect on its homeostasis. In this case, the hormone can activate both bone formation and resorption. Thus, PTH can ensure the conjugation of anabolic and catabolic processes, which is necessary for the renewal of bone tissue, which is had to function under constant mechanical stress. At the same time, the use of PTH in medical practice is rather small, despite its high potential as a basis for the treatment of various pathologies associated with impaired bone homeostasis. Presented review, describes the intracellular signaling cascades and molecular mechanisms that underlie the action of PTH on bone tissue cells, and intracellular signaling cascades are described. A separate section examines the cellular mechanisms of the action of PTH on bone homeostasis, discusses how the effect of the hormone on different types of cells provides an interface between the processes of synthesis and resorption. In addition, the review examines diseases associated with impaired bone homeostasis, as well as the role of PTH and impaired signaling in their etiology.

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

2020 ◽  
Author(s):  
Ludmila Brodetska ◽  
Larysa Natrus ◽  
Olha Lisakovska ◽  
Olexandr Kaniura ◽  
Liudmyla Iakovenko ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Tissue ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Active Form ◽  
Tooth Eruption ◽  
Control Group ◽  
Impacted Teeth ◽  
Tooth Impaction

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, 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-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.

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

2020 ◽  
Author(s):  
Ludmila Brodetska ◽  
Larysa Natrus ◽  
Olha Lisakovska ◽  
Olexandr Kaniura ◽  
Liudmyla Iakovenko ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Tissue ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Active Form ◽  
Tooth Eruption ◽  
Control Group ◽  
Impacted Teeth ◽  
Tooth Impaction

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.

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