Receptor Activator Of Nuclear Factor kappa-B Ligand Research Articles

Prophylactic and therapeutic effects of (6)-shogaol on alveolar bone loss in experimental periodontitis.

(6)-Shogaol is the most prevalent bioactive compound in ginger. The aim of this study was to examine both the prophylactic and therapeutic effects of (6)-shogaol in an experimental periodontitis model. Thirty-five male Wistar albino rats were divided into four groups. In the healthy group (n=5), no intervention was undertaken. In the periodontitis group (n=10), periodontitis was induced by ligature placement for 14 days. In the prophylaxis group (n=10), periodontitis was induced with ligature placement for 14 days, and during this time, 20 mg/kg/day of (6)-shogaol was administered via oral gavage. In the therapeutic group (n=10), periodontitis was induced with ligature placement for 14 days, and following the removal of the ligature, 20 mg/kg/day of (6)-shogaol was administered via oral gavage for 14 days. Alveolar bone loss was histometrically measured, and malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GP), nuclear factor kappa B (NF-κB), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) were immunohistochemically analyzed. Alveolar bone loss was significantly lower in the healthy group than in the remaining groups, as well as in the therapeutic group than in the periodontitis group (p<0.001). RANKL/OPG was significantly higher in the periodontitis group compared to the remaining groups and in the prophylaxis group compared to the therapeutic group (p<0.001). MDA was significantly lower in the healthy group than in the remaining groups (p<0.001). SOD was significantly lower in the periodontitis group than in the prophylaxis and therapeutic groups (p=0.039 and p=0.042, respectively). GP was significantly lower in the healthy group than in the prophylaxis and therapeutic groups (p=0.031 and p=0.002, respectively). The administration of (6)-shogaol modulated the RANKL/OPG balance and antioxidant status in rats with ligature-induced periodontitis.

Роль вітаміну D у функціонуванні кісткових клітин

The review summarizes current literature data on the importance of vitamin D in bone cell function. An analytical search was conducted in the PubMed, MEDLINE, Embase, Scopus, and Web of Science databases from January 1, 2018, to June 01, 2023. The vitamin D metabolite 1α,25(OH)2D3 plays an important role in the regulation of mineral homeostasis and bone metabolism. It has catabolic and anabolic actions on osteoblasts, osteocytes and mature osteoclasts. In this review, we describe the direct and indirect effects of 1α,25(OH)2D3 on the function of mesenchymal stromal cells (MSCs), osteoblasts, osteocytes, and osteoclasts. Among the targets of vitamin D action in bone cells are vitamin D receptor (VDR) and cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). In osteoblasts and MSCs with CYP27B1 knockout, cell proliferation and differentiation are impaired, and in osteoclasts, the resorption activity and lifespan of these cells are increased. The role of VDR in bone cells was demonstrated in normal and VDR-knockout animal models. The relationship between 1α,25(OH)2D3 – VDR signal transduction by bone cells and calcium balance was analyzed. In osteocytes, as well as in osteoblasts, 1α,25(OH)2D3 regulates the expression of RANKL (receptor activator of nuclear factor kappa-B ligand)), and additionally in osteocytes regulates the expression of FGF-23. The interaction of many other factors in bone cells has been shown to control the biological activity of 1α,25(OH)2D3. Thus, the effect of vitamin D on bone cells is in the phase of active research and requires an in-depth study of the features of its autocrine and paracrine effects. Identification of the molecular links of the mechanism of action of 1α,25(OH)2D3 on bone metabolism will provide a fundamental basis for approaches to the treatment of vitamin D deficiency diseases.

5′-Methylthioadenosine strongly suppresses RANKL-induced osteoclast differentiation and function via inhibition of RANK-NFATc1 signalling pathways

Excessive osteoclast-mediated bone resorption is a critical cause of osteoporosis affecting many aging people worldwide. 5′-Methylthioadenosine (MTA) is a natural sulfur-containing nucleoside normally produced in prokaryotes, plants, yeast, and higher eukaryotes via polyamine metabolism. MTA affects various physiological responses particularly the inflammatory pathway in both normal and cancerous cells and modulates the activation of nuclear factor-κB involved in the osteoclastogenesis signalling process. While several studies have reported that natural products possess anti-osteoclastogenesis phenolics and flavonoids, the effect of nucleoside derivatives on osteoclastogenesis remains limited. Therefore, this study aimed to explore the molecular mechanisms by which MTA affects pre-osteoclastic RAW 264.7 cells as a potential alleviation compound for inflammation-mediated bone loss. Osteoclasts were established by incubating RAW264.7 macrophage cells with receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor, the vital cytokines for activation of osteoclast differentiation. Cell viability was measured using MTT assays at 24, 48, and 72 h. The suppressive effect of MTA on RANKL-induced osteoclast differentiation and function was assessed using tartrate-resistant acid phosphatase (TRAP) analysis, qRT-PCR, and pit formation, Western blot, and immunofluorescence assays. MTA showed dose-dependent anti-osteoclastogenic activity by inhibiting TRAP-positive cell and pit formation and reducing essential digestive enzymes, including TRAP, cathepsin K, and matrix metallopeptidase 9. MTA was observed to suppress the osteoclast transduction pathway through (RANKL)-induced nuclear factor kappa-light-chain-enhancer of activated B cells (NFƘB); it attenuated NFƘB-P65 expression and down-regulated cFos proto-oncogene and nuclear factor of activated T cell c1 (NFATc1), the main regulators of osteoclasts. Moreover, the suppression of RANK (the initial receptor triggering several osteoclastogenic transduction pathways) was observed. Thus, this study highlights the potential of MTA as an effective therapeutic compound for restoring bone metabolic disease by inhibiting the RANK-NFATc1 signal pathway.

Denosumab versus pamidronate in the treatment of osteolytic bone metastases secondary to breast cancer: a multi-institutional analysis

Background Breast cancer is the most common cancer in women and most often metastasizes to the bone, resulting in skeletal-related events (SREs). Bone-modifying agents (BMAs) including denosumab, a monoclonal antibody against the receptor activator of nuclear factor kappa-b ligand (RANKL), and pamidronate, a bisphosphonate, are used to prevent these adverse events. Methods To analyze the efficacy of denosumab versus pamidronate, we used the TriNetX research platform and compared the outcomes of pathologic fracture, spinal cord compression, and overall 5-year survival rate between each pharmacotherapy. Results There was no statistical difference for an increased risk in pathological fractures (2.7% vs. 2.8%, P = 0.88), spinal cord compression (2.6% vs. 2.7%, P = 0.88), or 5-year survival rate (45.5% vs. 52.4%, P = 0.78) for the denosumab cohort versus the pamidronate cohort. Conclusion Since neither therapy showed an increased risk in the adverse effects measured in this study, factors such as patient preference, financial costs, and additional side effects of each medication should be taken into consideration when choosing a therapy for bone metastases in patients with breast cancer.

Inflammation is responsible for systemic bone loss in patients with seropositive rheumatoid arthritis treated with rituximab.

We investigated the effect of rituximab on systemic bone metabolism in patients with seropositive rheumatoid arthritis (RA). Twenty seropositive patients with RA were enrolled and administered one cycle of rituximab. If RA became active for > 6 months after the first rituximab cycle, a second cycle was initiated; otherwise, no additional treatment was administered. Patients were divided into two groups according to the number of rituximab treatment cycles. In patients treated with a second cycle, the total hip bone mineral density (BMD) was clinically low, whereas the serum levels of receptor activator of nuclear factor kappa-B ligand (RANKL) were increased at 12 months. BMD in patients treated with one cycle did not change at 12 months, whereas serum RANKL levels decreased at all time points. DAS28 activity improved in both groups from baseline to 4 months; however, from 4 to 12 months, DAS28 activity worsened in the develgroup with the second cycle but remained stable in the group with one cycle. Systemic inflammation, reflected by increased disease activity, may be responsible for the increase in RANKL levels, which causes systemic bone loss in rituximab-treated patients with RA. Although rituximab affects inflammation, it does not seem to alter systemic bone metabolism in RA.

The effect of vitamin D on the early clinical manifestations of menopausal syndrome and the production of cytokines, involved in bone remodeling

Introduction. The problem of early manifestations of menopausal syndrome is due to the high prevalence among postmenopausal women, a wide range of clinical manifestations, a sharp decrease in the quality of life, not always sufficient effectiveness of menopausal hormone therapy (MHT) in the presence of restrictions on its use.The aim. To evaluate the dynamics of clinical manifestations of menopausal syndrome and to determine the pathogenetic effects of vitamin D preparation when used in combination with menopausal hormone therapy in women of early postmenopausal age with menopausal syndrome.Materials and methods. 154 women were examined, of which 81 were characterized by the presence of clinical manifestations of menopausal syndrome. All women with menopausal syndrome received menopausal hormone therapy with estradiol and didrogesterone drug for 6 months, while 39 women additionally also took the vitamin D drug. Before and after therapy in patients with menopausal syndrome, the prevalence of symptoms of the Green scale was assessed. Concentrations of 25(OH) D, osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-B ligand (RANKL) were determined in the blood serum of all women.Results and discussion. The use of MHT by women with menopausal syndrome leads to a decrease in the frequency of registration of a number of symptoms of the Green scale (p &lt; 0.05). At the same time, a decrease in the frequency of registration of individual complaints is found only in the group of women who, along with MYT, received a vitamin D preparation (p &lt; 0.05). Taking the vitamin D preparation is accompanied by an increase in its initially reduced serum concentrations to normal values (p &lt; 0.001). The addition of cholecalciferol to the complex therapy of menopausal syndrome ensures the normalization of RANKL levels by reducing its production in the dynamics of treatment (p &lt; 0.05) A decrease in the concentration of RANKL in response to the complex intake of a hormonal drug and cholecalciferol caused higher OPG/RANKL index values in the basic group by the end of therapy than in women of the comparison group (p &lt; 0.01).Conclusions. The obtained effects of vitamin D preparation when prescribed in combination with menopausal hormone therapy (reduction of the frequency of symptoms of menopausal syndrome, reduction of initially elevated levels of RANKL) indicate the expediency of its use in the treatment of early manifestations of menopausal syndrome.

Extracellular Signal-Regulated Kinases Play Essential but Contrasting Roles in Osteoclast Differentiation.

Bone homeostasis is regulated by the balanced actions of osteoblasts that form the bone and osteoclasts (OCs) that resorb the bone. Bone-resorbing OCs are differentiated from hematopoietic monocyte/macrophage lineage cells, whereas osteoblasts are derived from mesenchymal progenitors. OC differentiation is induced by two key cytokines, macrophage colony-stimulating factor (M-CSF), a factor essential for the proliferation and survival of the OCs, and receptor activator of nuclear factor kappa-B ligand (RANKL), a factor for responsible for the differentiation of the OCs. Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinases (ERKs), p38, and c-Jun N-terminal kinases, play an essential role in regulating the proliferation, differentiation, and function of OCs. ERKs have been known to play a critical role in the differentiation and activation of OCs. In most cases, ERKs positively regulate OC differentiation and function. However, several reports present conflicting conclusions. Interestingly, the inhibition of OC differentiation by ERK1/2 is observed only in OCs differentiated from RAW 264.7 cells. Therefore, in this review, we summarize the current understanding of the conflicting actions of ERK1/2 in OC differentiation.

Desmarestia anceps Montagne modulates inflammatory response in experimental periodontitis in male Wistar rats

ObjectiveDesmarestia anceps Montagne (D. anceps) seaweed has been shown to play a range of biologic activities, such as anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effects of D. anceps on pathogenesis of ligature-induced experimental periodontitis in rats. DesignFifty-four male Wistar rats were randomly divided into six groups. Doses of D. anceps (100 and 200 mg/kg) were administered for 14 days to animals with or without ligature-induced periodontitis, in order to compare to control groups (vehicle solution). Morphometric registration of alveolar bone loss and histological analysis were conducted. Inflammatory cells were counted on hematoxylin-eosin-stained slides. Immunohistochemical expressions for interleukin-1 beta (IL-1β), tumor necrosis factor (TNF-α), receptor activator of nuclear factor kappa-Β ligand (RANKL) and bone morphogenetic protein 2 (BMP-2) were evaluated. ResultsAlveolar bone loss was higher in groups exposed to ligature-induced periodontitis, but no significant differences were observed comparing different treatment and control groups. Animals that received D. anceps extracts showed significant lower counts of inflammatory cells. D. anceps promoted increased expression of BMP-2 and inhibited IL-1β, TNF-α and RANKL. ConclusionD. anceps modulates inflammatory response in experimental periodontitis in rats. Further pharmacological and immunological analyses are warranted.

Bioactive Self-Regulated Liquified Microcompartments to Bioengineer Bone-Like Microtissues.

Designing a microenvironment that drives autonomous stromal cell differentiation toward osteogenesis while recapitulating the complexity of bone tissue remains challenging. In the current study, bone-like microtissues are created using electrohydrodynamic atomization to form two distinct liquefied microcapsules (mCAPs): i) hydroxypyridinone (HOPO)-modified gelatin (GH mCAPs, 7.5% w/v), and ii) HOPO-modified gelatin and dopamine-modified gelatin (GH+GD mCAPs, 7.5%+1.5% w/v). The ability of HOPO to coordinate with iron ions at physiological pH allows the formation of a semipermeable micro-hydrogel shell. In turn, the dopamine affinity for calcium ions sets a bioactive milieu for bone-like microtissues. After 21 days post encapsulation, GH and GH+GD mCAPs potentiate autonomous osteogenic differentiation of mesenchymal stem cells accompanied by collagen type-I gene upregulation, increased alkaline phosphatase (ALP)expression, and formation of mineralized extracellular matrix. However, the GH+GD mCAPs show higher levels of osteogenic markers starting on day 14, translating into a more advanced and organized mineralized matrix. The GH+GD system also shows upregulation of the receptor activator of nuclear factor kappa-B ligand (RANK-L) gene, enabling the autonomous osteoclastic differentiation of monocytes. These catechol-based mCAPs offer a promising approach to designing multifunctional and autonomous bone-like microtissues to study in vitro bone-related processes at the cell-tissue interface, angiogenesis, and osteoclastogenesis.

Effect of Liraglutide on Osteoporosis in a Rat Model of Type 2 Diabetes Mellitus: A Histological, Immunohistochemical, and Biochemical Study.

Diabetic osteoporosis (DOP) is a diabetic complication associated with a significant disability rate. Liraglutide, a glucagon-like peptide-1 receptor agonist, is a promising and innovative drug for type 2 diabetes mellitus (T2DM), with potential therapeutic implications for bone disorders. This investigation examined the impact of liraglutide on osteoporosis in rats with T2DM and studied the influence of vitamin D receptor Bsm1 polymorphism on liraglutide-induced outcomes. Thirty rats were divided into control, T2DM induced by a combination of a high-fat diet and 25 mg/kg streptozotocin, and T2DM-liraglutide (T2DM treated with 0.4 mg/kg/day liraglutide) groups. After 8 weeks of liraglutide treatment, femurs and blood samples were obtained from all rats for subsequent investigations. Diabetes induced a remarkable rise in the serum levels of receptor activator of nuclear factor kappa B ligand (RANKL) and C-telopeptide of type I collagen (CTX-1) associated with a remarkable decline in osteocalcin and osteoprotegerin (OPG). Impaired bone architecture was also demonstrated by light and scanning electron microscopic study. The immune expression of OPG was down-regulated, while RANKL was up-regulated. Interestingly, the administration of liraglutide ameliorated the previous changes induced by diabetes mellitus. In conclusion, liraglutide can prevent DOP, mostly due to liraglutide's ability to increase bone growth, while inhibiting bone resorption.

Effectiveness of anthocyanin-rich foods on bone remodeling biomarkers of middle-aged and older adults at risk of osteoporosis: a systematic review, meta-analysis, and meta-regression.

Current osteoporosis pharmacological treatment has undesirable side effects. There is increasing focus on naturally derived food substances that contain phytonutrients with antioxidant effects in promoting health and regulating immune response. This review aims to systematically evaluate the effectiveness of anthocyanin-rich foods on bone remodeling biomarkers in middle-aged and older adults (≥40 y old) at risk of osteoporosis. Randomized controlled trials were searched on 8 bibliographic databases of PubMed, Embase, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Food Science and Technology Abstracts, Cochrane Library, and ProQuest. Thirteen studies were included in the meta-analysis. Receptor activator of nuclear factor kappa-B ligand (RANKL) is exhibited from osteoblastic cells that gathered osteoclasts to bone sites for bone resorption, accelerating bone loss. Anthocyanin-rich food consumption showed statistically nonsignificant effects, with no substantial heterogeneity on bone remodeling biomarkers. However, there was a significant increase in lumbar spine L1-L4 bone mineral density. Mild-to-small effects were seen to largely favor the consumption of anthocyanin-rich foods. Berries (d = -0.44) have a larger effect size of RANKL than plums (d = 0.18), with statistically significant subgroup differences. Random-effects meta-regression found body mass index, total attrition rate, total energy, and dietary carbohydrate and fat intake were significant covariates for the effect size of RANKL. All outcomes had low certainty of evidence. Anthocyanin-rich foods may improve bone health in middle-aged and older adults at risk of osteoporosis. This review contributes to the growing interest in nutrient-rich foods as a low-cost and modifiable alternative to promote human health and reduce disease burden. Future high-quality studies with larger sample sizes and longer treatment durations are required to fully understand the effect of anthocyanin-rich foods on bone health. PROSPERO registration no. CRD42022367136.

Mechanical force application and inflammation induce osteoclastogenesis by independent pathways.

To investigate the functional changes of PDL fibroblasts in the presence of mechanical force, inflammation, or a combination of force and inflammation. Inflammatory supernatants were prepared by inoculating human neutrophils with Porphyromonas gingivalis. Primary human PDL fibroblasts (PDLF), gingival fibroblasts (GFs), and osteoblasts (Saos2) were then exposed to the inflammatory supernatants. Orthodontic force on the PDLFs was simulated by centrifugation. Analyses included cell proliferation, cell viability, cell cycle, and collagen expression, as well as osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL) expression. Mechanical force did not affect PDLF viability, but it increased the metabolic rate compared to resting cells. Force application shifted the PDLF cell cycle to the G0/G1 phase, arresting cell proliferation and leading to elevated collagen production, mild OPG level elevation, and robust RANKL level elevation. Including an inflammatory supernatant in the presence of force did not affect PDLF viability, proliferation, or cytokine expression. By contrast, the inflammatory supernatant increased RANKL expression in GFs, but not in Saos2 cells. Applying mechanical force significantly affects PDLF function. Although inflammation had no effect on PDLF or Saos2 cells, it promoted RANKL expression in GF cells. Within the limitations of the in vitro model, the results suggest that periodontal inflammation and mechanical forces could affect bone catabolism through effects on different cell types, which may culminate in synergistic bone resorption.

Bee Pollen Stimulated BMP2 and RANK Signaling Pathway in Osteoprogenitors and Improved Bone Mineralization in Rat Model of Femur Fracture

Objectives Bee pollen (BP) contains isoflavonoids and minerals that can be effective in bone repair, stimulation of osteoprogenitors, differentiation of osteoblasts, and inhibition of osteoclasts. For this purpose, in the present study, BP was used to stimulate osteogenesis in an animal model of a femur fracture. Materials and Methods After induction of the femur fracture model, 80 Wistar rats in eight groups ( n = 10) were studied as follows. Normal control group (0.5 cc of distilled water, DW/gavage/90 days), BP group (200 mg/kg BP/daily/gavage/90 days), fracture (FX-0.5 cc of distilled water/gavage/90 days), FX group treated with 100 and 200 mg/kg BP (100 and 200 mg/kg BP/daily/gavage/90 days), FX group treated with osteocare (OC) syrup (1 mL/day/gavage/90 days) and combinatorial FX groups treated with BP and OC syrup (100 and 200 mg/kg BP plus 1 mL OC/daily/gavage/90 days). On the 30th, 60th, and 90th days, radiography of the lesion was done. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry during the mentioned days. At the end of the study, blood calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP), along with the activity of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) enzymes, and nitric oxide levels, were measured. Calcitonin and parathyroid hormone levels were measured with enzyme-linked immunosorbent assay (ELISA) kits. In order to evaluate the stimulation of osteoprogenitors, the expression of osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), and bone morphogenetic protein-2 (BMP-2) genes and proteins in bone tissue was measured. Results The evaluations of this study showed that BP could improve BMD parameters through stimulation of the OPG/RANK/BMP-2 pathway. BP also improved serum levels of biochemical factors (Ca, P, and ALP) and hormones related to osteogenesis. Conclusion BP can be used for bone fractures and disorders related to osteoporosis.

Denosumab use reduces risk of rheumatoid arthritis in patients with osteoporosis.

To investigate the protective effect of osteoporosis medications on the risk of developing rheumatoid arthritis (RA) in patients with osteoporosis. We conducted a retrospective cohort study from 1 January, 2011 to 31 March, 2023. There was a total of 971901 patients from a hospital-based population in Taiwan. In this cohort, there was a total of 17065 osteoporosis patients with or without pathological fracture. In these patients, 7180 patients were osteoporosis medication users, and 9605 patients were non-osteoporosis medication users, after exclusion of previous RA. The risk of RA in the patients with osteoporosis medications was assessed, and stratified by sex and different medications, including bisphosphonates, denosumab, raloxifene and teriparatide. Patients with osteoporosis medication use had a reduced risk of RA compared with non-osteoporosis medication users [adjusted hazard ratio (aHR)=0.484, 95%CI: 0.270-0.867, p<0.05), after adjusting for age, comorbidites and medications. Specifically, patients with ever use of bisphosphonates (n=2069) or denosumab (n=4510) had a reduced risk of RA (aHR=0.405, 95%CI: 0.173-0.951, p<0.05, and aHR=0.394, 95%CI: 0.192-0.809, p<0.05, respectively). Notably, patients that only used denosumab (n=2938) had a further reduced risk of RA (aHR=0.32, 95%CI: 0.12-0.83, p<0.05), particularly in female patients (aHR=0.26, 95%CI: 0.09-0.74, p<0.05). Patients taking raloxifene or teriparatide did not have a significantly reduced risk of RA. Denosumab use reduces the risk of RA in patients with osteoporosis. Receptor activator of nuclear factor kappa B ligand (RANKL) mediated osteoclast joint damage may be involved in the pathogenesis of RA during the preclinical stage.

Effect of age on orthodontic tooth movement in mice

Background/purposeThe number of middle-aged and elderly orthodontic patients is increasing due to changes in age composition. It is important to investigate the detailed mechanisms of bone remodeling in orthodontic tooth movement (OTM) in the elderly. However, there are few reports on the mechanism of tooth movement in the elderly. The purpose of the present study was to analyze OTM and osteoclastogenesis in aged mice and to elucidate the mechanism. Materials and methodsIt has been reported that tumor necrosis factor (TNF)-α plays an important role in osteoclast formation and OTM. First, 8-week-old and 78-week-old male C57BL/6J mice were subcutaneously injected with TNF-α into the calvaiae, and micro-CT, tartrate-resistant acid phosphatase (TRAP) staining, and real-time PCR were performed to evaluate osteoclast formation and bone resorption. Furthermore, osteoclastogenesis by TNF-α and receptor activator of nuclear factor-kappa B ligand (RANKL) using bone marrow cells was evaluated in vitro. Finally, a nickel-titanium closed-coil spring was attached, mesial movement of the maxillary left first molar was performed, and tooth movement distance and osteoclast formation were evaluated. ResultsCompared to 8-week-old mice, 78-week-old mice had decreased TNF-α-induced bone resorption, osteoclastogenesis, and TRAP and cathepsin K expression in the calvariae. In vitro osteoclast formation also decreased in 78-week-old mice. Furthermore, tooth movement distance and osteoclastogenesis were reduced. ConclusionOTM decreased in aged mice, which was shown to be caused by a decrease in osteoclastogenesis. Therefore, it was suggested that it is necessary to keep in mind that tooth movement may be suppressed when treating elderly patients.

The role of miR-433-3p in vascular calcification in type 2 diabetic patients: targeting WNT/β-Catenin and RANKL/RANK/OPG signaling pathways

BackgroundVascular calcification (VC) is a major predictor of cardiovascular diseases that represent the principal cause of mortality among type-2 diabetic patients. Accumulating data suggest the vital role of some microRNAs on vascular calcification as an epigenetic regulator. Thus, we assessed herein, the role of serum miR-433-3p in vascular calcification in type-2 diabetic patients.MethodsTwenty healthy subjects (control group) and forty diabetic patients (20 without VC and 20 with VC) were involved in the study. miR-433-3p gene expression was measured. Runx2, Dickkopf-1 (DKK1), β-catenin, Receptor activator of nuclear factor kappa-B ligand (RANKL), and osteoprotegerin (OPG) levels in serum were assessed by ELISA technique.ResultsDiabetes patients had significantly lower levels of miR-433-3p expression in comparison to the control group, with the lowest levels being found in diabetic patients with VC. Furthermore, Runx2, β-catenin, and RANKL levels were significantly increased with concomitant lower DKK1 and OPG levels detected in the two diabetic groups especially those with VC.ConclusionCollectively, the study documented that down-regulation of miR-433-3p may contribute to the development of VC through activating WNT/β-Catenin and RANKL/RANK/OPG signaling pathways.

Electrospun sandwich mesh structures loaded with naringenin and vitamin K2 polycaprolactone/gelatin nanofibers synergistically promote bone regeneration

Osteoblasts and osteoclasts play a crucial role in the dynamically coupled balance during bone regeneration and remodeling. They complement and restrict each other in the human body. Decreased osteoblasts lead to insufficient bone formation or excessive formation of osteoclasts, leading to increased bone resorption, which will destroy the structure of the bone tissue. This will greatly increase the risk of diseases such as osteoporosis and nonunions caused by bone defects.Herein, gelatin and polycaprolactone were used as substrates, and biomaterial membranes with mesh and sandwich structures were constructed using the electrospinning technology. Naringenin was loaded into the shell, and vitamin K2 was loaded into the core layer of the nanofibrous membrane. The biocompatibility and osteogenic capacity of the membranes were assessed in vitro using mouse bone marrow mesenchymal stem cells (BMSCs). During osteoclast induction, the receptor activator of nuclear factor kappa-Β ligand (RANKL) was used to coculture RAW264.7 cells with various materials. The regulatory effect of various membranes on osteoclast growth was evaluated by detecting the expression levels of osteoclast-related genes and proteins in the cells.Subsequently, we constructed a model of a rat skull defect and implanted different membranes into the defect. Then, we evaluated the new bone formation in the defect using histological staining and micro-computed tomography after 4 and 8 weeks. The results of in vitro experiments confirmed that the incorporation of naringenin and vitamin K2 stimulated the expression of osteogenesis-related genes and the secretion of osteogenesis-related proteins. Simultaneously, the results showed that naringenin and vitamin K2 inhibited the formation and growth of osteoclasts. Therefore, naringenin and vitamin K2 have a synergistic effect in promoting bone growth and regulating osteoclast growth.

Interleukin-21 knockout reduces bone loss in ovariectomized mice by inhibiting osteoclastogenesis.

Estrogen deficiency accelerates osteoporosis in elderly women. However, the role of IL-21 in postmenopausal osteoporosis remains unclear. Female wild-type (WT) C57BL/6 and IL-21 knockout (KO) mice were used for ovariectomy (OVX). Here, IL-21 levels were significantly increased in the serum and bone tissues of WT-OVX mice. The trabecular bone space of the femur was significantly increased, and the bone mass was reduced in OVX mice, accompanied by a significant decrease in the maximum load, energy absorption, and elastic modulus indices. In contrast, IL-21 knockout effectively alleviated the effects of OVX on bone mass. Serum TRACP-5b and receptor activator of nuclear factor kappa B ligand (RANKL) levels and osteoclastogenesis were significantly higher in OVX mice than in sham mice, while serum TRACP-5b and RANKL levels and osteoclastogenesis were significantly decreased in IL-21 KO+OVX mice compared to WT+OVX mice. IL-21 knockdown reduces TRACP-5b, RANKL, and osteoclastogenesis, effectively preventing bone resorption and alleviating the progression of OVX-induced osteoporosis.

Impact of 3D collagen-based model and hydrostatic pressure on periodontal ligament fibroblast: A morpho-biochemical analysis

This study developed a customized hydrostatic pressure-based loading environment to investigate the effect of static hydrostatic pressure on the periodontal ligament fibroblasts (PDLf) in a three-dimensional (3D) collagen-based model. The cylindrical tissue constructs were comprised of PDL fibroblast cells seeded in type I collagen matrices and divided into three experimental groups: Control (no load), low-load (∼0.07 kPa), and high-load (∼60 kPa), all subjected to 24 h of experimental duration. Cells in the 3D construct were stained with fluorophore-conjugated antibodies for cytoskeletal protein F-actin and matricellular protein periostin. Cell culture supernatant was assessed for receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) expression. Transmission electron microscopy examined the contact between the cells and the collagen matrix. Ultrastructural changes in the 3D collagen matrix were also analyzed using scanning electron microscopy. Experiments were performed in triplicates, and data was analyzed using one-way ANOVA (p < 0.05). The 3D PDLf constructs from the low-load group demonstrated the highest levels of homogeneous cell distribution and higher expression of F-actin and periostin with enhanced interaction with the matrix. The collagen matrix in this group showed more closely packed fibers forming thicker bundles when compared to the control and the high-load 3D PDLf constructs. Nonuniform cell distribution with decreased expression of F-actin and periostin was observed in the control and high-load PDLf constructs. The high-load group showed the highest RANKL/OPG expression. This study demonstrated low-level hydrostatic pressure's role in regulating PDLf functions and extracellular matrix response, while excessive hydrostatic pressure may be detrimental to PDL fibroblast cell function.

Effect of bromelain on periodontal destruction and alveolar bone in rats with experimental periodontitis.

Several substances that have anti-inflammatory, antiproteinase, and anti-infective properties have been evaluated as modulators of the inflammatory response in periodontal disease. However, evidence for the anti-inflammatory and antioxidative activities of bromelain is limited. This study evaluated the impact of systemically administered bromelain on the progression of experimental periodontitis. Four equal groups of 32 Wistar albino rats were created as follows (n=8): control, periodontitis+saline, periodontitis+5mg/kg/day bromelain, and periodontitis+10mg/kg/day bromelain. To quantify the resorption of bone and bone volume/tissue volume, bone surface / bone volume, and connectivity, lower jawbones were fixed and then scanned using microcomputed tomography (micro CT). Blood samples were taken to measure the macrophage colony-stimulating factor(M-CSF) concentrations, receptor activator of nuclear factor kappa-Β ligand (RANKL), osteoprotegerin (OPG), tumor necrosis factor-alpha (TNF-α), matrix metalloproteinase-8 (MMP-8), interleukin-6(IL-6), glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological assessments were made to examine the tissue. Treatment with bromelain improved the healing of the periodontium by decreasing the number of leukocytes and ligament deterioration in the gingival connective tissue and by supporting reintegration with alveolar bone. Bromelain used in ligature-induced periodontitis reduced alveolar bone (AB) resorption as measured by microCT; reduced inflammatory parameters such as IL-6 and TNF-α; regulated oxidative-antioxidative processes by increasing GPx and SOD and reducing MDA levels; and regulated AB modeling by decreasing M-CSF, RANKL, and MMP-8 and increasing OPG levels. Bromelain may be an option in periodontal therapy by regulating cytokine levels, improving the healing process, and reducing bone resorption and oxidative stress.