Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with...Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.展开更多
AIM To assess serum levels of RANK-ligand(RANKL) and osteoprotegerin(OPG) as biomarkers for periprosthetic joint infection(PJI) and compare their accuracy with standard tests.METHODS One hundred and twenty patients pr...AIM To assess serum levels of RANK-ligand(RANKL) and osteoprotegerin(OPG) as biomarkers for periprosthetic joint infection(PJI) and compare their accuracy with standard tests.METHODS One hundred and twenty patients presenting with a painful total knee or hip arthroplasty with indication for surgical revision were included in this prospective clinical trial. Based on standard diagnostics(joint aspirate, microbiological, and histological samples) and Musculoskeletal Infection Society consensus classification,patients were categorized into PJI, aseptic loosening,and control groups. Implant loosening was assessed radiographically and intraoperatively. Preoperative serum samples were collected and analyzed for RANKL, OPG, calcium, phosphate, alkaline phosphatase(AP), and the bone-specific subform of AP(b AP). Statistical analysis was carried out, testing for significant differences between the three groups and between stable and loose implants. RESULTS All three groups were identical in regards to age, gender, and joint distribution. No statistically significant differences in the serum concentration of RANKL(P = 0.16) and OPG(P = 0.45) were found between aseptic loosening and PJI, with a trend towards lower RANKL concentrations and higher OPG concentrations in the PJI group. The RANKL/OPG ratio was significant for the comparison between PJI and non-PJI(P = 0.005). A ratio > 60 ruled out PJI in all cases(specificity: 100%, 95%CI: 89, 11% to 100.0%) but only 30% of non-PJI patients crossed this threshold. The positive predictive value remained poor at any cut-off. In the differentiation between stable and loose implants, none of the parameters measured(calcium, phosphate, AP, and b AP) showed a significant difference, and only AP and b AP measurements showed a tendency towards higher values in the loosened group(with P = 0.09 for AP and P = 0.19 for b AP). CONCLUSION Lower RANKL and higher OPG concentrations could be detected in PJI, without statistical significance.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women.Screening and management of GDM and gestational hypertensi...BACKGROUND Gestational diabetes mellitus(GDM)raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women.Screening and management of GDM and gestational hypertension(GH)in pregnancy helps to control and reduce these risks and prevent adverse effects on mothers and their fetuses.Currently,the majority criteria used for screening of diabetes mellitus is oral glucose tolerance tests,and blood pressure test is usually used for the screening and diagnosis of hypertension.However,these criteria might not anticipate or detect all GDM or GH cases.Therefore,new specific predictive and diagnostic tools should be evaluated for this population.This study selected three biomarkers of osteoprotegerin(OPG),interleukin(IL)and hepatocyte growth factor(HGF)for GDM and GH predication and diagnosis.AIM To explore the feasibility of changes in placental and serum OPG,IL and HGF as tools for prediction and diagnosis of diabetes and hypertension in pregnant women.METHODS From January 2018 to January 2019,44 pregnant women with GDM and GH were selected as an observation group,and 44 healthy pregnant women were selected as a control group in the same period.Serum OPG,IL and HGF were compared between the two groups.RESULTS The levels of OPG and HGF in the observation group were lower than in the control group,and the level of IL-1βwas higher in the observation group than in the control group(all P<0.05).Furthermore,OPG and HGF were negatively associated with gestational diabetes and gestational hypertension,while IL-1βwas positively associated with GDM complicated with GH(all P<0.05).CONCLUSION The evaluation of serum OPG,HGF and IL-1βlevels in patients with coexistent gestational diabetes complicated with hypertension can predict the degree of disease and play an important role in the follow-up treatment and prognosis prediction.展开更多
Objective To evaluate the effect of alendronate on osteoprotegerin(OPG)and receptor of activator of nuclear factor κB-ligand(RANKL)expression in human marrow stroma cells(hMSCs)in vitro.Methods hMSCs were isolated fr...Objective To evaluate the effect of alendronate on osteoprotegerin(OPG)and receptor of activator of nuclear factor κB-ligand(RANKL)expression in human marrow stroma cells(hMSCs)in vitro.Methods hMSCs were isolated from human marrow,cultured in vitro,and randomly divided into two groups:alendronate group,hMSCs culture fluid containing 1×10-7mol/L alendronate;control group,no special treatment but culturing hMSCs in DMEM.Two weeks after treatment,the expressions of OPG and RANKL were evaluated by RT-PCR and Western blot.Results hMSCs became uniform spindle-shaped fibroblasts.As cells proliferated,they formed colonies and showed whirlpool arrangement.After one week's treatment,hMSCs in alendronate group had reduced processes and gradually showed disc shape,which did not happen in control group but kept fibroblast shape and just increased in density.In RT-PCR,the ratio of OPG/RANKL in alendronate group and control group was 8.77±1.16 and 4.58±1.27,respectively.In Western blot,the ratio of OPG/RANKL in alendronate group and control group was 2.58±0.47 and 1.52±0.32,respectively.The ratio of OPG/RANKL was higher in alendronate group than in control group(P<0.01).Conclusion Alendronate enhances OPG expression and inhibits RANKL expression of hMSCs in vitro.展开更多
Objective: To investigate the effect of recombinant human osteoprotegerin combined with tinidazole on mice with periodontitis and the effect on serum RANKL and MCP-1 levels. Methods: 80 SPF-cleaned mice were randomly ...Objective: To investigate the effect of recombinant human osteoprotegerin combined with tinidazole on mice with periodontitis and the effect on serum RANKL and MCP-1 levels. Methods: 80 SPF-cleaned mice were randomly divided into 4 groups, 20 each, model group, tinidazole group and recombinant human osteoprotegerin group were modeled by Kimura et al., and tinidazole group received tinidazole. After intragastric administration, the recombinant human osteoprotegerin group was injected with recombinant human osteoprotegerin in the periodontal pocket according to the tinidazole group. The periodontal changes of the four groups of mice were observed and recorded, and the gingival rating was performed. Epithelial tissue morphology was observed by hematoxylin-eosin (HE) staining. Serum levels of IL-4, IL-6, RANKL and MCP-1 were measured by enzyme-linked immunosorbent assay. Results:After the intervention, the model group developed severe inflammatory reactions, including redness, hemorrhage, and deep periodontal pockets. The teeth were significantly loosened. The mice in the tinidazole group and the recombinant human osteoprotegerin group recovered substantially, and the gingival rating of the recombinant human osteoprotegerin group was better than that. The tinidazole group and the model group (P<0.05). The results of HE staining showed that the model group had edema, vasodilation and a large amount of inflammatory infiltration. The epithelial structure of the mice in the tinidazole group and the recombinant human osteoprotegerin group was intact and arranged closely and orderly. After intervention, the IL-4 in the tinidazole group and the recombinant human osteoprotegerin group was significantly higher than the model group and IL-6 was significantly lower than the model group (P<0.05), and the recombinant human osteoprotegerin group IL-4 was significantly higher after the intervention. IL-6 was significantly lower in the tinidazole group than in the tinidazole group (P<0.05). After the intervention, the tinidazole group and the recombinant human osteoprotegerin group were significantly reduced, and the recombinant human osteoprotegerin group RAKNL and MCP-1 were significantly lower than the model group (P>0.05). Conclusion: Recombinant human osteoprotegerin combined with tinidazole has a better therapeutic effect on gums and teeth in mice with periodontitis, and can lower the levels of RAKNL and MCP-1 in serum, inhibit bone resorption and protect teeth.展开更多
Objective: To investigate the influence of Notch signaling on osteoprotegerin(OPG)expression in a human oral squamous cell carcinoma cell line.Methods: Activation of Notch signaling was performed by seeding cells on J...Objective: To investigate the influence of Notch signaling on osteoprotegerin(OPG)expression in a human oral squamous cell carcinoma cell line.Methods: Activation of Notch signaling was performed by seeding cells on Jagged1 immobilized surfaces. In other experiments, a g-secretase inhibitor was added to the culture medium to inhibit intracellular Notch signaling. OPG m RNA and protein were determined by real-time PCR and ELISA, respectively. Finally, publicly available microarray database analysis was performed using connection up- or down-regulation expression analysis of microarrays software.Results: Jagged1-treatment of HSC-4 cells enhanced HES1 and HEY1 m RNA expression, confirming the intracellular activation of Notch signaling. OPG m RNA and protein levels were significantly suppressed upon Jagged1 treatment. Correspondingly, HSC-4 cells treated with a g-secretase inhibitor resulted in a significant reduction of HES1 and HEY1 m RNA levels, and a marked increase in OPG protein expression was observed.These results implied that Notch signaling regulated OPG expression in HSC-4 cells.However, Jagged1 did not alter OPG expression in another human oral squamous cell carcinoma cell line(HSC-5) or a human head and neck squamous cell carcinoma cell line(HN22).Conclusions: Notch signaling regulated OPG expression in an HSC-4 cell line and this mechanism could be cell line specific.展开更多
Background Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquit...Background Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquitously and abundantly in many tissues and cell types including vascular cells, the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) and upregulated during vascular lesion formation. Methods and Results We documented, by Northern blot analysis,that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats (SI-IR) compared to Wistar-Kyoto rats (WKY). In addition, we found that the expression of Angiotensin II (Ang II)type I receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC. Furthermore, Ang II potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1R signaling pathway. Conclusions OPG expression was substantially greater in SHR VSMC, suggesting that OPG may be an important determinant of vascular remodeling in SHR.展开更多
Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering ...Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering RNA(siRNA)eukaryotic expression vector targeted transforming growth factor βⅡ receptor(TGF-β RⅡ)was constructed and transfected into T cells.HPDL cells with T cells transfected with siRNA or not were placed in the culture medium that had been added with lipopolysaccharide(LPS)and baicalin.The obtained solution was divided into six groups according to the components(group Ⅰ:HPDL cells+LPS+T cells transfected with siRNA1+baicalin;group Ⅱ:HPDL cells+LPS+T cells transfected with siRNA1;group Ⅲ:HPDL cells+LPS+T cells+baicalin;group Ⅳ:HPDL cells+LPS+T cells;group Ⅴ:HPDL cells+baicalin;group Ⅵ:HPDL cells)and was cultured for 48 hours.RT-PCR was used to observe the effect of baicalin on the expression of OPG-RANKL in HPDL cells.Results The ratio of RANKL/OPG in group Ⅰ was lower than that in group Ⅱ(P<0.01)and higher than that in group Ⅲ(P<0.01);The ratio of RANKL/OPG in group Ⅲ was lower than that in group Ⅳ(P<0.01);the ratio of RANKL/OPG in group Ⅳ was higher than that in group Ⅵ(P<0.01);the ratio of RANKL/OPG in group Ⅴ was lower than that in group Ⅵ(P<0.05).Conclusion ① Baicalin could decrease the ratio of RANKL/OPG in HPDL cells.② The TGF-β signaling transduction plays an important role in the effect of baicalin on the RANKL/OPG ratio in HPDL cells.③ Baicalin acts not only through TGF-β to regulate RANKL/OPG in HPDL cells,but also through other pathways.展开更多
Background: High blood pressure is associated with adverse morphological and functional changes in the cardiovascular system, including left ventricular hypertrophy (LVH). Osteoprotegerin (OPG) is a member of the tumo...Background: High blood pressure is associated with adverse morphological and functional changes in the cardiovascular system, including left ventricular hypertrophy (LVH). Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily of cytokines. X-ray repair cross-complementing protein 3 (XRCC3) is involved in the repair pathway for double-strand breaks (DSBs). We assessed the association of osteoprotegerin and XRCC3 gene polymorphisms with the occurrence of left ventricular hypertrophy in hypertensive patients. Patients and methods: The study included 50 hypertensive patients: 25 with LVH (group A) and 25 without LVH (group B). All cases were subjected to complete history taking and clinical examination. ECG and echocardiography were done. LV mass was calculated to detect the presence or absence of LV hypertrophy. DNA was extracted from blood samples, and then, each DNA sample was amplified in PCRs, to detect osteoprotogrin and XRCC3 gene polymorphisms. Results: Mean age in the cases in group A is 63.12 years and in group B was 58.24 years with statistically significant difference between the two groups. The duration of the disease and SBP revealed statistically significant difference between the two groups. The LV mass index and E/A ratio revealed high statistically significant difference between the two groups. OPG sequence revealed no statistically significant difference between the two groups, but XRCC3 sequence revealed statistically significant difference. The age was a risk factor for LVH. Conclusion: Osteoprotogrin and XRCC3 genes polymorphism mutations may be associated with left ventricular hypertrophy in hypertensive patients.展开更多
Osteoprotegerin (OPG) is a protein produced by many cell types that has the remarkable property of inhibiting bone loss. It does this by binding to the key bone resorptive cytokine, receptor activator of NF-kB ligand ...Osteoprotegerin (OPG) is a protein produced by many cell types that has the remarkable property of inhibiting bone loss. It does this by binding to the key bone resorptive cytokine, receptor activator of NF-kB ligand (RANKL). This cytokine is produced mainly by osteoblastic cells and is instrumental in osteoclast differentiation. If the ratio of RANKL:OPG increases, bone resorption increases and results in bone loss in diseases such osteoporosis, rheumatoid arthritis and hypercalcaemia of malignancy. Hence, if drugs can be found that increase OPG, this will decrease the activity of osteoclasts and therefore bone resorption. Statins are cholesterol lowering drugs that have recently been shown to increase bone formation in rodents. It was hypothesised from this finding that this could be due to an increase in OPG production. If these commonly prescribed drugs could be used to prevent bone loss or to increase bone formation then this may prove a useful means of reducing fracture risk in patients. Treating Saos-2 osteoblast-like cells in vitro with mevastatin increased OPG production and secretion through the mevalonate pathway. A failure of geranylgeranylation of Rho and/or farnesylation of Ras proteins leads to an increase in PI-3K activation then AKT activation leading to several different signaling pathways such as MAPK’s and NF-kB. NF-kB and p38MAPK inhibitors prevented the statin stimulation of OPG but not the decrease in cell number, suggesting that statins regulate OPG secretion via PI-3K, p38MAPK and NF-kB.展开更多
Vascular calcifications are commonly observed in patients with chronic kidney disease(CKD) and contribute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although ...Vascular calcifications are commonly observed in patients with chronic kidney disease(CKD) and contribute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although the pathogenetic mechanisms are not yet fully elucidated, recent evidence suggests a link between bone metabolism and the development and progression of vascular calcifications. Moreover, accumulating data indicate that receptor activator of nuclear factor κB ligand/osteoprotegerin axis which plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation. Further studies are required to establish the prognostic significance of the above biomarkers as predictors of the presence and severity of vascular calcifications in CKD patients and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifications.展开更多
AIM:To investigate risk factors for low bone mineral density(BMD) in celiac disease(CD) patients,focusing on circulating autoantibodies against osteoprotegerin(OPG).METHODS:Seventy asymptomatic CD adult patients on gl...AIM:To investigate risk factors for low bone mineral density(BMD) in celiac disease(CD) patients,focusing on circulating autoantibodies against osteoprotegerin(OPG).METHODS:Seventy asymptomatic CD adult patients on gluten-free diet(GFD) and harbouring persistent negative CD-related serology were recruited.Conventional risk factors for osteoporosis(e.g.,age,sex,menopausal status,history of fractures,smoke,and body mass index) were checked and BMD was assessed by dual energy X ray absorptiometry.Serum calcium and parathyroid hormone(PTH) levels were evaluated.Thirty-eight patients underwent repeat duodenal biopsy.Serum samples from a selected sub-group of 30 patients,who were also typed for human leukocyte antigen(HLA) DQ2 and DQ8 haplotype,were incubatedwith homodimeric recombinant human OPG and tested by western blotting with an anti-OPG antibody after immunoprecipitation.RESULTS:Despite persistent negative CD-related serology and strict adherence to GFD,49 out of the 70(74%) patients displayed low BMD.Among these patients,13(24%) showed osteoporosis and 36(76%) osteopenia.With the exception of age,conventional risk factors for osteoporosis did not differ between patients with normal and low BMD.Circulating serum calcium and PTH levels were normal in all patients.Duodenal mucosa healing was found in 31(82%) out of 38 patients who underwent repeat duodenal biopsy with 20(64%) still displaying low BMD.The remaining 7 patients had an incomplete normalization of duodenal mucosa with 6(84%) showing low BMD.No evidence of circulating antibodies against OPG was found in the serum of 30 celiac patients who were tested for,independent of BMD,duodenal histology,and HLA status.CONCLUSION:If any,the role of circulating autoantibodies against OPG in the pathogenesis of bone derangement in patients with CD is not a major one.展开更多
文摘Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease(NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome(Met S), like insulin resistance(IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, Met S, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin(OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesityrelated comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of Met S as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.
基金Supported by The"Deutsche Arthrose-Hilfe e.V.",No.P192-A362-2009-12
文摘AIM To assess serum levels of RANK-ligand(RANKL) and osteoprotegerin(OPG) as biomarkers for periprosthetic joint infection(PJI) and compare their accuracy with standard tests.METHODS One hundred and twenty patients presenting with a painful total knee or hip arthroplasty with indication for surgical revision were included in this prospective clinical trial. Based on standard diagnostics(joint aspirate, microbiological, and histological samples) and Musculoskeletal Infection Society consensus classification,patients were categorized into PJI, aseptic loosening,and control groups. Implant loosening was assessed radiographically and intraoperatively. Preoperative serum samples were collected and analyzed for RANKL, OPG, calcium, phosphate, alkaline phosphatase(AP), and the bone-specific subform of AP(b AP). Statistical analysis was carried out, testing for significant differences between the three groups and between stable and loose implants. RESULTS All three groups were identical in regards to age, gender, and joint distribution. No statistically significant differences in the serum concentration of RANKL(P = 0.16) and OPG(P = 0.45) were found between aseptic loosening and PJI, with a trend towards lower RANKL concentrations and higher OPG concentrations in the PJI group. The RANKL/OPG ratio was significant for the comparison between PJI and non-PJI(P = 0.005). A ratio > 60 ruled out PJI in all cases(specificity: 100%, 95%CI: 89, 11% to 100.0%) but only 30% of non-PJI patients crossed this threshold. The positive predictive value remained poor at any cut-off. In the differentiation between stable and loose implants, none of the parameters measured(calcium, phosphate, AP, and b AP) showed a significant difference, and only AP and b AP measurements showed a tendency towards higher values in the loosened group(with P = 0.09 for AP and P = 0.19 for b AP). CONCLUSION Lower RANKL and higher OPG concentrations could be detected in PJI, without statistical significance.
基金Supported by Hainan Province Major Program of Science and Technology Projects 2017,No.ZDKJ2017007.
文摘BACKGROUND Gestational diabetes mellitus(GDM)raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women.Screening and management of GDM and gestational hypertension(GH)in pregnancy helps to control and reduce these risks and prevent adverse effects on mothers and their fetuses.Currently,the majority criteria used for screening of diabetes mellitus is oral glucose tolerance tests,and blood pressure test is usually used for the screening and diagnosis of hypertension.However,these criteria might not anticipate or detect all GDM or GH cases.Therefore,new specific predictive and diagnostic tools should be evaluated for this population.This study selected three biomarkers of osteoprotegerin(OPG),interleukin(IL)and hepatocyte growth factor(HGF)for GDM and GH predication and diagnosis.AIM To explore the feasibility of changes in placental and serum OPG,IL and HGF as tools for prediction and diagnosis of diabetes and hypertension in pregnant women.METHODS From January 2018 to January 2019,44 pregnant women with GDM and GH were selected as an observation group,and 44 healthy pregnant women were selected as a control group in the same period.Serum OPG,IL and HGF were compared between the two groups.RESULTS The levels of OPG and HGF in the observation group were lower than in the control group,and the level of IL-1βwas higher in the observation group than in the control group(all P<0.05).Furthermore,OPG and HGF were negatively associated with gestational diabetes and gestational hypertension,while IL-1βwas positively associated with GDM complicated with GH(all P<0.05).CONCLUSION The evaluation of serum OPG,HGF and IL-1βlevels in patients with coexistent gestational diabetes complicated with hypertension can predict the degree of disease and play an important role in the follow-up treatment and prognosis prediction.
基金supported by the National Natural Science Foundation of China(No.30600624)
文摘Objective To evaluate the effect of alendronate on osteoprotegerin(OPG)and receptor of activator of nuclear factor κB-ligand(RANKL)expression in human marrow stroma cells(hMSCs)in vitro.Methods hMSCs were isolated from human marrow,cultured in vitro,and randomly divided into two groups:alendronate group,hMSCs culture fluid containing 1×10-7mol/L alendronate;control group,no special treatment but culturing hMSCs in DMEM.Two weeks after treatment,the expressions of OPG and RANKL were evaluated by RT-PCR and Western blot.Results hMSCs became uniform spindle-shaped fibroblasts.As cells proliferated,they formed colonies and showed whirlpool arrangement.After one week's treatment,hMSCs in alendronate group had reduced processes and gradually showed disc shape,which did not happen in control group but kept fibroblast shape and just increased in density.In RT-PCR,the ratio of OPG/RANKL in alendronate group and control group was 8.77±1.16 and 4.58±1.27,respectively.In Western blot,the ratio of OPG/RANKL in alendronate group and control group was 2.58±0.47 and 1.52±0.32,respectively.The ratio of OPG/RANKL was higher in alendronate group than in control group(P<0.01).Conclusion Alendronate enhances OPG expression and inhibits RANKL expression of hMSCs in vitro.
文摘Objective: To investigate the effect of recombinant human osteoprotegerin combined with tinidazole on mice with periodontitis and the effect on serum RANKL and MCP-1 levels. Methods: 80 SPF-cleaned mice were randomly divided into 4 groups, 20 each, model group, tinidazole group and recombinant human osteoprotegerin group were modeled by Kimura et al., and tinidazole group received tinidazole. After intragastric administration, the recombinant human osteoprotegerin group was injected with recombinant human osteoprotegerin in the periodontal pocket according to the tinidazole group. The periodontal changes of the four groups of mice were observed and recorded, and the gingival rating was performed. Epithelial tissue morphology was observed by hematoxylin-eosin (HE) staining. Serum levels of IL-4, IL-6, RANKL and MCP-1 were measured by enzyme-linked immunosorbent assay. Results:After the intervention, the model group developed severe inflammatory reactions, including redness, hemorrhage, and deep periodontal pockets. The teeth were significantly loosened. The mice in the tinidazole group and the recombinant human osteoprotegerin group recovered substantially, and the gingival rating of the recombinant human osteoprotegerin group was better than that. The tinidazole group and the model group (P<0.05). The results of HE staining showed that the model group had edema, vasodilation and a large amount of inflammatory infiltration. The epithelial structure of the mice in the tinidazole group and the recombinant human osteoprotegerin group was intact and arranged closely and orderly. After intervention, the IL-4 in the tinidazole group and the recombinant human osteoprotegerin group was significantly higher than the model group and IL-6 was significantly lower than the model group (P<0.05), and the recombinant human osteoprotegerin group IL-4 was significantly higher after the intervention. IL-6 was significantly lower in the tinidazole group than in the tinidazole group (P<0.05). After the intervention, the tinidazole group and the recombinant human osteoprotegerin group were significantly reduced, and the recombinant human osteoprotegerin group RAKNL and MCP-1 were significantly lower than the model group (P>0.05). Conclusion: Recombinant human osteoprotegerin combined with tinidazole has a better therapeutic effect on gums and teeth in mice with periodontitis, and can lower the levels of RAKNL and MCP-1 in serum, inhibit bone resorption and protect teeth.
基金Supported by a Faculty Research Grant(No.DRF-59010)Faculty of Dentistry,Chulalongkorn University and the 2012 Research Chair Grant,Thailand National Science and Technology Development Agency
文摘Objective: To investigate the influence of Notch signaling on osteoprotegerin(OPG)expression in a human oral squamous cell carcinoma cell line.Methods: Activation of Notch signaling was performed by seeding cells on Jagged1 immobilized surfaces. In other experiments, a g-secretase inhibitor was added to the culture medium to inhibit intracellular Notch signaling. OPG m RNA and protein were determined by real-time PCR and ELISA, respectively. Finally, publicly available microarray database analysis was performed using connection up- or down-regulation expression analysis of microarrays software.Results: Jagged1-treatment of HSC-4 cells enhanced HES1 and HEY1 m RNA expression, confirming the intracellular activation of Notch signaling. OPG m RNA and protein levels were significantly suppressed upon Jagged1 treatment. Correspondingly, HSC-4 cells treated with a g-secretase inhibitor resulted in a significant reduction of HES1 and HEY1 m RNA levels, and a marked increase in OPG protein expression was observed.These results implied that Notch signaling regulated OPG expression in HSC-4 cells.However, Jagged1 did not alter OPG expression in another human oral squamous cell carcinoma cell line(HSC-5) or a human head and neck squamous cell carcinoma cell line(HN22).Conclusions: Notch signaling regulated OPG expression in an HSC-4 cell line and this mechanism could be cell line specific.
文摘Background Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquitously and abundantly in many tissues and cell types including vascular cells, the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) and upregulated during vascular lesion formation. Methods and Results We documented, by Northern blot analysis,that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats (SI-IR) compared to Wistar-Kyoto rats (WKY). In addition, we found that the expression of Angiotensin II (Ang II)type I receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC. Furthermore, Ang II potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1R signaling pathway. Conclusions OPG expression was substantially greater in SHR VSMC, suggesting that OPG may be an important determinant of vascular remodeling in SHR.
基金supported by the Foundation of Stomatology Hospital,Xi'an Jiaotong University
文摘Objective To study the effect of baicalin on the expression of receptor activator of nuclear factor-κB ligand(RANKL)and osteoprotegerin(OPG)in cultured human periodontal ligament(HPDL)cells.Methods Small interfering RNA(siRNA)eukaryotic expression vector targeted transforming growth factor βⅡ receptor(TGF-β RⅡ)was constructed and transfected into T cells.HPDL cells with T cells transfected with siRNA or not were placed in the culture medium that had been added with lipopolysaccharide(LPS)and baicalin.The obtained solution was divided into six groups according to the components(group Ⅰ:HPDL cells+LPS+T cells transfected with siRNA1+baicalin;group Ⅱ:HPDL cells+LPS+T cells transfected with siRNA1;group Ⅲ:HPDL cells+LPS+T cells+baicalin;group Ⅳ:HPDL cells+LPS+T cells;group Ⅴ:HPDL cells+baicalin;group Ⅵ:HPDL cells)and was cultured for 48 hours.RT-PCR was used to observe the effect of baicalin on the expression of OPG-RANKL in HPDL cells.Results The ratio of RANKL/OPG in group Ⅰ was lower than that in group Ⅱ(P<0.01)and higher than that in group Ⅲ(P<0.01);The ratio of RANKL/OPG in group Ⅲ was lower than that in group Ⅳ(P<0.01);the ratio of RANKL/OPG in group Ⅳ was higher than that in group Ⅵ(P<0.01);the ratio of RANKL/OPG in group Ⅴ was lower than that in group Ⅵ(P<0.05).Conclusion ① Baicalin could decrease the ratio of RANKL/OPG in HPDL cells.② The TGF-β signaling transduction plays an important role in the effect of baicalin on the RANKL/OPG ratio in HPDL cells.③ Baicalin acts not only through TGF-β to regulate RANKL/OPG in HPDL cells,but also through other pathways.
文摘Background: High blood pressure is associated with adverse morphological and functional changes in the cardiovascular system, including left ventricular hypertrophy (LVH). Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily of cytokines. X-ray repair cross-complementing protein 3 (XRCC3) is involved in the repair pathway for double-strand breaks (DSBs). We assessed the association of osteoprotegerin and XRCC3 gene polymorphisms with the occurrence of left ventricular hypertrophy in hypertensive patients. Patients and methods: The study included 50 hypertensive patients: 25 with LVH (group A) and 25 without LVH (group B). All cases were subjected to complete history taking and clinical examination. ECG and echocardiography were done. LV mass was calculated to detect the presence or absence of LV hypertrophy. DNA was extracted from blood samples, and then, each DNA sample was amplified in PCRs, to detect osteoprotogrin and XRCC3 gene polymorphisms. Results: Mean age in the cases in group A is 63.12 years and in group B was 58.24 years with statistically significant difference between the two groups. The duration of the disease and SBP revealed statistically significant difference between the two groups. The LV mass index and E/A ratio revealed high statistically significant difference between the two groups. OPG sequence revealed no statistically significant difference between the two groups, but XRCC3 sequence revealed statistically significant difference. The age was a risk factor for LVH. Conclusion: Osteoprotogrin and XRCC3 genes polymorphism mutations may be associated with left ventricular hypertrophy in hypertensive patients.
文摘Osteoprotegerin (OPG) is a protein produced by many cell types that has the remarkable property of inhibiting bone loss. It does this by binding to the key bone resorptive cytokine, receptor activator of NF-kB ligand (RANKL). This cytokine is produced mainly by osteoblastic cells and is instrumental in osteoclast differentiation. If the ratio of RANKL:OPG increases, bone resorption increases and results in bone loss in diseases such osteoporosis, rheumatoid arthritis and hypercalcaemia of malignancy. Hence, if drugs can be found that increase OPG, this will decrease the activity of osteoclasts and therefore bone resorption. Statins are cholesterol lowering drugs that have recently been shown to increase bone formation in rodents. It was hypothesised from this finding that this could be due to an increase in OPG production. If these commonly prescribed drugs could be used to prevent bone loss or to increase bone formation then this may prove a useful means of reducing fracture risk in patients. Treating Saos-2 osteoblast-like cells in vitro with mevastatin increased OPG production and secretion through the mevalonate pathway. A failure of geranylgeranylation of Rho and/or farnesylation of Ras proteins leads to an increase in PI-3K activation then AKT activation leading to several different signaling pathways such as MAPK’s and NF-kB. NF-kB and p38MAPK inhibitors prevented the statin stimulation of OPG but not the decrease in cell number, suggesting that statins regulate OPG secretion via PI-3K, p38MAPK and NF-kB.
文摘Vascular calcifications are commonly observed in patients with chronic kidney disease(CKD) and contribute to the excessive cardiovascular morbidity and mortality rates observed in these patients populations. Although the pathogenetic mechanisms are not yet fully elucidated, recent evidence suggests a link between bone metabolism and the development and progression of vascular calcifications. Moreover, accumulating data indicate that receptor activator of nuclear factor κB ligand/osteoprotegerin axis which plays essential roles in the regulation of bone metabolism is also involved in extra-osseous bone formation. Further studies are required to establish the prognostic significance of the above biomarkers as predictors of the presence and severity of vascular calcifications in CKD patients and of cardiovascular morbidity and mortality. Moreover, randomized clinical trials are needed to clarify whether inhibition of osteoclast activity will protect from vascular calcifications.
文摘AIM:To investigate risk factors for low bone mineral density(BMD) in celiac disease(CD) patients,focusing on circulating autoantibodies against osteoprotegerin(OPG).METHODS:Seventy asymptomatic CD adult patients on gluten-free diet(GFD) and harbouring persistent negative CD-related serology were recruited.Conventional risk factors for osteoporosis(e.g.,age,sex,menopausal status,history of fractures,smoke,and body mass index) were checked and BMD was assessed by dual energy X ray absorptiometry.Serum calcium and parathyroid hormone(PTH) levels were evaluated.Thirty-eight patients underwent repeat duodenal biopsy.Serum samples from a selected sub-group of 30 patients,who were also typed for human leukocyte antigen(HLA) DQ2 and DQ8 haplotype,were incubatedwith homodimeric recombinant human OPG and tested by western blotting with an anti-OPG antibody after immunoprecipitation.RESULTS:Despite persistent negative CD-related serology and strict adherence to GFD,49 out of the 70(74%) patients displayed low BMD.Among these patients,13(24%) showed osteoporosis and 36(76%) osteopenia.With the exception of age,conventional risk factors for osteoporosis did not differ between patients with normal and low BMD.Circulating serum calcium and PTH levels were normal in all patients.Duodenal mucosa healing was found in 31(82%) out of 38 patients who underwent repeat duodenal biopsy with 20(64%) still displaying low BMD.The remaining 7 patients had an incomplete normalization of duodenal mucosa with 6(84%) showing low BMD.No evidence of circulating antibodies against OPG was found in the serum of 30 celiac patients who were tested for,independent of BMD,duodenal histology,and HLA status.CONCLUSION:If any,the role of circulating autoantibodies against OPG in the pathogenesis of bone derangement in patients with CD is not a major one.
