جستجوی مقالات مرتبط با کلیدواژه « rankl » در نشریات گروه « پزشکی »

We aimed to compare the changes in the two salivary biomarkers, RANKL and RANK, among patients with healthy gingiva on reduced periodontium versus generalized periodontitis stages II and III.

Study subjects were divided into three groups: (1) healthy periodontium (control group) (n=15), (2) generalized periodontitis stages II and III (n=30), and (3) healthy gingiva on reduced periodontium (n=30). Salivary levels of RANKL and RANK were assessed using an enzyme-linked immunosorbent assay. Data analysis was done by the one-way ANOVA and the Tukey post hoc test using R software.

There was a statistically significant difference among the three study groups regarding salivary levels of the RANKL (P < 0.001) and RANK (P < 0.001). A Post hoc test showed that the difference between salivary levels of the RANKL (P=0.50) and RANK (P=0.86) among periodontitis groups and healthy gingiva in the reduced periodontium group was not statistically significant.

High salivary levels of RANKL and RANK in comparison with healthy gingiva are not necessarily associated with the active phase of periodontal disease and progressive bone destruction.

Vitamin D is an important steroid that can regulate bone metabolism including osteoclast (OC) differentiation. Transient receptor potential cation channel subfamily V member 5 (TRPV5), is a calcium channel protein involved in OC differentiation. However, the impact of vitamin D on TRPV5 expression during OC differentiation is not clear.

To determine if 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) regulates the expression of TRPV5 during OC differentiation.

Bone marrow mononuclear macrophage (BMMs) were induced to differentiate intoOCwith or without treatment with 10 nM1,25(OH)2D3. The expression levels of vitamin D receptor (VDR) and TRPV5 were examined. The expression of several OC markers, including tartrate resistant acid phosphatase (TRAP), carbonic anhydrase II (Ca II), cathepsin K (CTSK), and vacuolar-type H+-ATPase (V-ATPase) were also detected.

We found that theVDRwas expressed in murine bonemarrow-derived macrophages at the early stage of OCdifferentiation. TRPV5 expression was increased during OC differentiation, which was down-regulated by 1,25(OH)2D3 after a prolonged exposure. The 1,25(OH)2D3 and TRPV5 inhibitors inhibited OC differentiation.

1,25(OH)2D3 can inhibit TRPV5 expression as well as TRPV5 inhibitors during OC differentiation. This suggests that
1,25(OH)2D3 may suppress OC differentiation by inhibiting TRPV5 expression.

To investigate the effect of cocoa on orthodontic tooth movement (OTM) rate, osteoprotegerin (OPG), and receptor activator of nuclear factor κ β ligand (RANKL) levels after OTM. A total of 24 Sprague-Dawley rats were included in the study. They were equally divided into two groups: cocoa and control. The upper incisors of all rats were subjected to 35 cN orthodontic force and moved distally with a stainless steel 3-spin coil spring. During OTM, the cocoa group was given 4.8 g of unsweetened cocoa once a day. At 4 subsequent time points (0, 1, 7, and 14 days), the OTM rate was determined by measuring the distance between the mesial tips using a digital caliper, while OPG and RANKL levels were examined based on their gingival crevicular fluid through specific enzyme-linked immunosorbent assay (ELISA). Data gathered were analyzed through independent t-test (P<0.05). The OTM rate of the cocoa group was significantly higher than that of the control group on days 1, 7, and 14 (P<0.05). ELISA analysis revealed that the OPG level was significantly lower on day 14. Furthermore, the RANKL level was significantly higher on days 0, 1, and 7 for the cocoa group compared with the control group (P<0.05). These results indicate that cocoa has the potential effect to modulate the OTM rate by inducing osteoclastogenesis, which suppresses the OPG level and stimulates the RANKL level, in rats.

The study aimed to uncover the underlying mechanism linking wear particles to osteoclast differentiation, and we explored the effect of titanium particles of different sizes on CD147 expression and autophagy in macrophages.
Effects of titanium particles on CD147 and RANKL mRNA were detected by QPCR; protein level of CD147 and Beclin-1 were detected by Western blot; soluble RANKL were detected by ELISA. To determine the effect of CD147 and autophagy, KG-1a cells were transfected with siRNA-CD147 or treated with autophagy inhibitor CQ (chloroquine), and then co-cultured with different sizes of titanium particles.
Our results showed that 0.2-1.2 µm and 1.2-10 µm titanium particles up-regulate CD147 to activate autophagy, which increase the level of soluble RANKL to promote osteoclastogenesis. Suppression of CD147 with siRNA could diminish particle-induced autophagy and soluble RANKL expression. In addition, CQ could dramatically reduce particle-induced soluble RANKL expression.
Our findings suggested a possible mechanism underlying wear debris-induced osteolysis and identified CD147 as a potential therapeutic target in aseptic loosening.

Chronic liver disease (CLD) affects millions of people and its impact on bone loss has become a subject of interest. Nitric oxide and endogenous opioids are suggested to increase during cholestasis/cirrhosis and may impact bone resorption by different mechanisms. The receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL)/osteoprotegerin (OPG) signaling pathway regulates bone resorption, but its role in metabolic bone disease subsequent to CLD is unknown. We aimed to investigate the involvement of nitrergic and opioidergic systems in bone loss relative to the RANK/RANKL/OPG pathway, in bile duct-ligated (BDL) rats. Eighty BDL/sham-operated (SO) rats received injections of 3 mg/kg/day Nω-Nitro-L-arginine methyl ester ± naltrexone (10 mg/kg/day) or saline for 28 days. Plasma bone turnover markers, OPG, RANK, and RANKL along with mRNA expression levels of the latter three were assessed. Plasma bone turnover markers and OPG level increased, but RANKL decreased in the BDL group compared with their SO controls (both: P ≤ 0.05). Administration of naltrexone reduced bone turnover markers and OPG level while increased RANKL content in comparison to BDL rats (P ≤ 0.05). As compared to untreated BDL rats, nitric oxide inhibition showed no effect on bone turnover marker i.e. OPG, RANK, and RANKL levels. BDL significantly increased RANK mRNA, but had no significant effect on RANKL and OPG mRNA expression. The lack of association between plasma levels and quantitative gene expression of RANKL and OPG suggests an indirect function of these markers in BDL rats. Considering that opioid receptor blockage by naltrexone in BDL animals caused a significant decrease in OPG and an increase in RANKL plasma contents, it could be postulated that the opioidergic system may have a regulatory effect on these bone markers.

The role of host response in periodontitis pathogenesis is confirmed, and it is well established that immune response plays a major role in the alveolar bone destruction. In the investigation of these responses, the role of receptor activator of the nuclear factor‑kB ligand (RANKL)‑osteoprotegerin (OPG) system is the most promising. Smoking can affect the RANKL‑OPG system in a manner that will further enhance bone loss in periodontitis. The aim of this study is to assess the serum, saliva, and gingival crevicular fluid (GCF) concentration of RANKL and OPG in smoker versus nonsmoker untreated chronic periodontitis (CP) patients.

Thirty‑nine subjects were included in the present cross‑sectional study: 29 systemically healthy CP male patients(15 smokers, 14 nonsmokers) and 10 systemically and periodontally healthy nonsmoker male subjects. Serum, GCF, and whole saliva samples were obtained from the subjects. The enzyme‑linked immunosorbent assay (ELISA) kits were used for assaying the concentrations of RANKL and OPG in the samples. The one‑way analysis of variance (ANOVA) test and the least significant difference (LSD) post hoc test were utilized to compare differences between the groups.

RANKL and OPG concentrations in saliva, serum, and GCF did not show any significant difference among all groups (P > 0.05). Salivary RANKL/OPG ratios were significantly higher in the nonsmoker CP group than in the healthy control group (P > 0.05) but they were not statistically significant among smoker periodontitis patients.

The salivary RANKL/OPG ratio was higher in nonsmokers with periodontitis in comparison with smoker periodontitis patients.

The aim of this study is to evaluate the effects of low-level neodymium-doped yttrium aluminium garnet (Nd:YAG) laser irradiation on orthodontic tooth movement and histological examination. Eleven male Wistar rats (aged 10 weeks) were included. To produce experimental tooth movement in rats, 10 g force was applied to maxillary first molars with nickel titanium closed coil springs. Right molars were irradiated with Nd:YAG laser on days 0, 1, 2, 3, 7, 10, 14, 17, 21 and 24, while un-irradiated left molars were used as control. Distance between mesial side of second molar and distal side of first molar was measured on μCT image during tooth movement and the rats were sacrificed 4 weeks after the initiation of tooth movement. The amount of tooth movement was significantly greater in the irradiation group (0.20 ± 0.06) than in the control group (0.14 ± 0.03) during the first week (P < 0.05). However, no statistically significant difference was found afterwards. There was a tendency of higher tartrate-resistant acid phosphatase (TRAP)-positive nuclei count in the pressure zones of the laser irradiation group, but it was not statistically significant. In immuno-histological examination, expressions of alkaline phosphatase (ALP) and receptor activator of nuclear factor kappa-B ligand (RANKL) were higher at the pressure site of the laser irradiation group than the control group, whereas there was no difference in osteoprotegerin (OPG) expression. The results suggest that low-level Nd:YAG laser may stimulate osteoclast and osteoblast activation and accelerate bone metabolism during tooth movement.

miR-125b has been identified as a tumor suppressor in many tumors, but its role in giant cell tumor (GCT) of bone remains poorly understood. The current study aimed to investigate the potential role and mechanism of miR-125b in GCT. Expression levels of miR-125b in GCT tissues were determined using RT-PCR. The cell proliferation was surveyed by direct cell counting, MTS and CCK-8, and the apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining assay. The target gene expression was determined using RT-PCR and western blot. Parathyroid hormone 1 receptor (PTH1R) 3’-UTR was cloned into luciferase reporter plasmid to confirm direct targeting. We found that miR-125b was significantly down-regulated in GCT tissues. Using both gain- and loss-of-function analyses, we further revealed that miR-125b suppressed GCT stromal cell proliferation and induced cell apoptosis. Furthermore, we revealed that PTH/PTHrP type 1 receptor is a direct and functional target of miR-125b. Our results suggest that miR-125b acts as a tumor suppressor through suppression of the PTH1R/RANKL signaling pathway. These findings contribute to our understanding of the functions of miR-125b in GCT.

There has been considerable inconsistency regarding the potential relationship between dyslipidemia and bone metabolism. The inflammatory stimulation through the receptor activator of the nuclear factor kappa-B ligand (RANKL)/ receptor activator of the nuclear factor kappa-B (RANK)/ osteoprotegerin (OPG) pathway could be the infrastructural mechanism for hypercholesterolemia-induced bone loss.In this study, we investigated the effect of dyslipidemia on RANKL and OPG alongside with pro-inflammatory cytokines. Thirty male C57Bl/6 mice (4 weeks old) were randomized to two purified diet groups (15 animals in each group), high fat, low carbohydrate diet (HFLCD) and its matched low fat, high carbohydrate diet (LFHCD). After 12 weeks of feeding in standard situations, the plasma concentration of lipid profile, interleukin (IL)1Beta,, IL-6, tumor necrosis factor-alpha (TNF-α) and RANKL, OPG, and RANKL: OPG ratio were measured.In the present study, although the body weight significantly increased during 12 weeks in HFLCD and LFHCD groups, there were no significant differences in food intake, food efficiency ratio and weight gain between the two groups. The LFHCD group had significantly higher median RANKL and RANKL/OPG ratio. There was no significant difference in plasma IL-1β, IL-6 and TNF-α concentration between LFHCD and HFLCD groups.These unexpected findings from LFHCD, that seem to be as a result of its higher carbohydrate proportion in comparison to HFLCD, implicate dietary carbohydrate rather than dietary fat as a more significant nutritional factor contributing to change in RANKL level and RANKL: OPG ratio.

Most of phenylketonuria (PKU) develops bone turnover impairment and low bone mineral density (BMD). Measurements of BMD reflect only bone mineral status but not the dynamics of bone turnover. Bone markers are a noninvasive tool useful for the assessment of bone formation and bone resorption processes. Our study was to assess the levels of bone markers in PKU in order to select a screen marker and detect the most specific marker which can be combined with BMD for appropriate follow up. Thirty three classic PKU patients were studied. BMD and bone mineral content (BMC) were measured. Total alkaline phosphatase (ALP), osteocalcin (OC) and carboxy-terminal propeptide of type I collagen (CICP), osteoprotegerin (OPG), receptor activator of nuclear factor κβ ligand (RANKL) and Deoxypyridinoline (DPD) were measured. Nineteen (57.6%) male and fourteen (42.4 %) female PKU patients were involved in the current study. Their mean age was 8.4±4.6 yrs and the age range 3-19 yrs. The control group consisted of twenty two (52.4%) males and twenty (47.6%) females. Their mean age was 8.5±3.3 yrs and th age range 2-17 yrs. Using the Z score values, there was a significant decrease of total BMC (TBMC-Z), BMD of the femoral neck BMD-FN-Z, BMD of lumbar vertebrae (BMD-L-Z), BMD-FN and DPD while RANKL increased. There was a negative correlation between CICP and TBMC and between CICP and BMD-L in these patients. Also, a negative correlation between ALP and TBMC and between ALP and BMD-L was observed. It was concluded that the ALP provides a good impression of the new bone formation in the PKU patients and it has a highly significant negative correlation with the many parameters of the bone mineral status beside the wide availability of inexpensive and simple methods. So a screening test and/or follow up for the PKU patients using ALP would be available. Once the level of ALP decrease is detected, one can combine it with BMD to explore the bone mineral status and with specific bone markers (OC, RANKL and DBD), to verify the dynamics of bone turnover. This schedule will reduce the risk of exposure of these patients to the risk hazards of DXA and limit its use only to a limited number of the highly suspected cases.

It often takes a relatively long period for a tooth with a large periradicular lesion to recover from bone destruction; therefore, it is necessary to develop additional approaches to serve as supplementary options to RCT. One possibility is to prevent the osteoclast-induced periapical bone destruction by inhibiting osteoclastogenesis. Recently, studies have proved the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system to be an important signal pathway regulating osteoclastogenesis, and inactivation of RANKL, which blocks the RANK/RANKL pathways, is critical in anti-bone resorption. The hypothesis: OPG, a natural decoy receptor for RANKL, may be a potential clinical anti-resorptive agent for apical periodontitis. Since OPG can block the RANK/RANKL pathways, it has been demonstrated to be a good candidate against bone destruction; its local delivery through root canals may be an additional option for treatment of apical periodontitis with large periradicular lesion.Evaluation of the hypothesis: OPG is easy to produce, store and use. Using a large animal study model, recombinant OPG could be incorporated into degradable carriers such as microspheres, micelle, and delivered into experimental induced periradicular lesions in the animals by controlled release, where it can relieve bone destruction by inhibiting osteoclastogenesis and osteoclast function. As OPG is a natural protein and clinical delivery as part of RCT treatment is easy and simple, the application of OPG may provide a new avenue for the treatment of apical periodontitis with large periradicular lesion.