BACKGROUND Matrix Gla protein(MGP)is a vitamin K dependent peptide which has an established role in suppression of vascular calcification.Recent studies have pointed to a possible link between immunomodulatory effect ...BACKGROUND Matrix Gla protein(MGP)is a vitamin K dependent peptide which has an established role in suppression of vascular calcification.Recent studies have pointed to a possible link between immunomodulatory effect of MGP and inflammatory bowel disease(IBD).AIM To compare plasma levels of dephosphorylated and uncarboxylated MGP(dpucMGP)between IBD patients and controls.METHODS This cross-sectional study was conducted on 70 patients with IBD(30 patients with ulcerative colitis and 40 patients with Crohn’s disease)and 60 age and gender matching healthy controls.Plasma dp-ucMGP levels were analyzed from blood samples by CLIA method using IDS-iSYS InaKtif MGP(Immunodiagnostic Systems,Frankfurt,Germany)according to the manufacturer's instructions.fecal calprotectin(FC)levels were determined from stool samples by turbidimetric immunoassay method using Bühlmann fecal calprotectin turbo assay(Bühlmann Laboratories Aktiengesellschaft,Schonenbuch,Switzerland).Other parameters were analyzed according to the standard laboratory procedures.RESULTS Plasma levels of dp-ucMGP were significantly higher in patients with IBD compared to the healthy control group(629.83±124.20 pmol/mL vs 546.7±122.09 pmol/mL,P<0.001),and there was no significant difference between patients with Crohn’s disease and patients with ulcerative colitis(640.02±131.88 pmol/mL vs 616.23±113.92 pmol/mL,P=0.432).Furthermore,a significant positive correlation of plasma dp-ucMGP levels was found with both FC levels(r=0.396,P<0.001)and high sensitivity C-reactive protein(hsCRP)levels(r=0.477,P<0.001).Moreover,in the total study population a significant positive correlation was found between dp-ucMGP with age(r=0.210,P=0.016)and waist circumference(r=0.264,P=0.002).Multiple linear regression analysis showed that dp-ucMGP levels retained significant association with FC(β±SE,0.06±0.02,P=0.003).CONCLUSION Study results support experimental data of MGP immunomodulatory IBD effect and indicate potential involvement in the pathophysiology of the disease,and possibly extraintestinal manifestations.展开更多
BACKGROUND Osteoporosis is a systemic bone disease characterized by decreased bone mass,impaired bone mass,and reduced bone strength that leads to increased bone fragility and fracture.Type 2 diabetes mellitus(T2DM)co...BACKGROUND Osteoporosis is a systemic bone disease characterized by decreased bone mass,impaired bone mass,and reduced bone strength that leads to increased bone fragility and fracture.Type 2 diabetes mellitus(T2DM)complicated with osteoporosis is a common systemic metabolic bone disease,and reduced bone mass and bone strength are considered the main clinical features;however,the pathogenesis of this disease has not been fully clarified.Its occurrence is considered related to sex,age,and genetic factors.There are many risk factors for diabetes complicated with osteoporosis.Therefore,exploring these risk factors will help prevent it.AIM To investigate the relationships among serum glucagon-like peptide-1(GLP-1)levels,matrix Gla protein(MGP)levels,and diabetes with osteoporosis.METHODS Sixty patients with T2DM complicated with osteoporosis confirmed by the endocrinology department of our hospital were selected as the case group.Sixty T2DM patients with bone loss were selected as the control group.Sixty healthy participants were selected as the healthy group.The general data,bone mineral density index,and bone metabolic markers of the three groups were compared.The relationships among GLP-1 levels,MGP levels,and the bone mineral density index of the case group were analyzed using linear correlation analysis and a logistic regression model.RESULTS Differences in sex,smoking,and drinking among the case group,control group,and healthy group were not statistically significant(P>0.05).The mean age of the case group was older than those of the control and healthy groups(P<0.05).The body mass index,fasting plasma glucose level,HbA1c level,hypertension rate,and coronary heart disease rate of the case and control groups were higher than those of the healthy group(P<0.05).The serum GLP-1 and MGP levels of the case group were lower than those of the control and healthy groups;these differences were statistically significant(P<0.05).The serum GLP-1 and MGP levels of the control group were lower than those of the healthy group;these differences were statistically significant(P<0.05).The serum GLP-1 and MGP levels of the case group were significantly positively correlated with the bone mineral density values of the hip and lumbar spine(P<0.05).The results of the logistic regression model showed that age and duration of diabetes were independent risk factors for osteoporosis in diabetic patients(P<0.05)and that increased GLP-1 and MGP values were protective factors against osteoporosis in diabetic patients(P<0.05).CONCLUSION Serum GLP-1 and MGP levels of diabetic patients with osteoporosis were significantly decreased and positively correlated with bone mineral density and were independent risk factors for osteoporosis in diabetic patients.展开更多
Background:Matrix Gla protein(MGP)is a secreted protein contributed to the immunomodulatory functions of mesenchymal stromal cells.Microarray profiling found a significantly higher expression level of the extracellula...Background:Matrix Gla protein(MGP)is a secreted protein contributed to the immunomodulatory functions of mesenchymal stromal cells.Microarray profiling found a significantly higher expression level of the extracellular matrix gene MGP in patients with ulcerative colitis(UC).However,little is known about the role of MGP in UC and its upstream signaling regulation.This study aimed to identify the expression of MGP in UC and its upstream regulator mechanism.Methods:Colonicmucosa biopsies were obtained frompatients with UC and healthy controls.DNAmicroarray profiling was used to explore underlying genes correlating with UC development.Mice were fed with water containing different concentrations of dextran sodiumsulfate(DSS)to induce an experimental colitismodel.Colonic tissues were collected and evaluated using immunohistochemistry,immunoblot,real-time polymerase chain reaction,and chromatin immunoprecipitation assay.Bioinformatics analysis was performed to identify candidate MGP gene-promoter sequence and transcription-initiation sites.Luciferase-reporter gene assay was conducted to examine the potential transcription factor ofMGP gene expression.Results:The expression of MGP was significantly increased in colonic tissues from UC patients and DSS-induced colitis models,and was positively correlated with disease severity.Bioinformatics analysis showed a conserved binding site for Egr-1 in the upstream region of human MGP gene.The significantly higher level of Egr-1 gene expression was found in UC patients than in healthy controls.The activity of luciferase was significantly enhanced in the Egr-1 expression plasmid cotransfected group than in the control group and was further inhibited when co-transfected with the Egr-1 binding-site mutated MGP promoter.Conclusions:Up-regulated expression of MGP was found in UC patients and DSS-induced colitis.The expression of MGP can be regulated by Egr-1.展开更多
基质GLA蛋白(matrix gla protein MGP)是体内软骨内骨形成和血管内钙化的重要调节因子,是矿盐沉积的重要抑制物。近年来发现绝经后妇女在发生骨质疏松症的同时还常伴有血管的钙化,认为两者可能存在着密切的联系。MGP抑制血管钙化同时与...基质GLA蛋白(matrix gla protein MGP)是体内软骨内骨形成和血管内钙化的重要调节因子,是矿盐沉积的重要抑制物。近年来发现绝经后妇女在发生骨质疏松症的同时还常伴有血管的钙化,认为两者可能存在着密切的联系。MGP抑制血管钙化同时与骨代谢密切相关。笔者对MGP与绝经后骨质疏松症的关系进行了简要的综述。展开更多
文摘BACKGROUND Matrix Gla protein(MGP)is a vitamin K dependent peptide which has an established role in suppression of vascular calcification.Recent studies have pointed to a possible link between immunomodulatory effect of MGP and inflammatory bowel disease(IBD).AIM To compare plasma levels of dephosphorylated and uncarboxylated MGP(dpucMGP)between IBD patients and controls.METHODS This cross-sectional study was conducted on 70 patients with IBD(30 patients with ulcerative colitis and 40 patients with Crohn’s disease)and 60 age and gender matching healthy controls.Plasma dp-ucMGP levels were analyzed from blood samples by CLIA method using IDS-iSYS InaKtif MGP(Immunodiagnostic Systems,Frankfurt,Germany)according to the manufacturer's instructions.fecal calprotectin(FC)levels were determined from stool samples by turbidimetric immunoassay method using Bühlmann fecal calprotectin turbo assay(Bühlmann Laboratories Aktiengesellschaft,Schonenbuch,Switzerland).Other parameters were analyzed according to the standard laboratory procedures.RESULTS Plasma levels of dp-ucMGP were significantly higher in patients with IBD compared to the healthy control group(629.83±124.20 pmol/mL vs 546.7±122.09 pmol/mL,P<0.001),and there was no significant difference between patients with Crohn’s disease and patients with ulcerative colitis(640.02±131.88 pmol/mL vs 616.23±113.92 pmol/mL,P=0.432).Furthermore,a significant positive correlation of plasma dp-ucMGP levels was found with both FC levels(r=0.396,P<0.001)and high sensitivity C-reactive protein(hsCRP)levels(r=0.477,P<0.001).Moreover,in the total study population a significant positive correlation was found between dp-ucMGP with age(r=0.210,P=0.016)and waist circumference(r=0.264,P=0.002).Multiple linear regression analysis showed that dp-ucMGP levels retained significant association with FC(β±SE,0.06±0.02,P=0.003).CONCLUSION Study results support experimental data of MGP immunomodulatory IBD effect and indicate potential involvement in the pathophysiology of the disease,and possibly extraintestinal manifestations.
基金Supported by Jiangxi Provincial Health and Family Planning Commission“Science and Technology Plan”.
文摘BACKGROUND Osteoporosis is a systemic bone disease characterized by decreased bone mass,impaired bone mass,and reduced bone strength that leads to increased bone fragility and fracture.Type 2 diabetes mellitus(T2DM)complicated with osteoporosis is a common systemic metabolic bone disease,and reduced bone mass and bone strength are considered the main clinical features;however,the pathogenesis of this disease has not been fully clarified.Its occurrence is considered related to sex,age,and genetic factors.There are many risk factors for diabetes complicated with osteoporosis.Therefore,exploring these risk factors will help prevent it.AIM To investigate the relationships among serum glucagon-like peptide-1(GLP-1)levels,matrix Gla protein(MGP)levels,and diabetes with osteoporosis.METHODS Sixty patients with T2DM complicated with osteoporosis confirmed by the endocrinology department of our hospital were selected as the case group.Sixty T2DM patients with bone loss were selected as the control group.Sixty healthy participants were selected as the healthy group.The general data,bone mineral density index,and bone metabolic markers of the three groups were compared.The relationships among GLP-1 levels,MGP levels,and the bone mineral density index of the case group were analyzed using linear correlation analysis and a logistic regression model.RESULTS Differences in sex,smoking,and drinking among the case group,control group,and healthy group were not statistically significant(P>0.05).The mean age of the case group was older than those of the control and healthy groups(P<0.05).The body mass index,fasting plasma glucose level,HbA1c level,hypertension rate,and coronary heart disease rate of the case and control groups were higher than those of the healthy group(P<0.05).The serum GLP-1 and MGP levels of the case group were lower than those of the control and healthy groups;these differences were statistically significant(P<0.05).The serum GLP-1 and MGP levels of the control group were lower than those of the healthy group;these differences were statistically significant(P<0.05).The serum GLP-1 and MGP levels of the case group were significantly positively correlated with the bone mineral density values of the hip and lumbar spine(P<0.05).The results of the logistic regression model showed that age and duration of diabetes were independent risk factors for osteoporosis in diabetic patients(P<0.05)and that increased GLP-1 and MGP values were protective factors against osteoporosis in diabetic patients(P<0.05).CONCLUSION Serum GLP-1 and MGP levels of diabetic patients with osteoporosis were significantly decreased and positively correlated with bone mineral density and were independent risk factors for osteoporosis in diabetic patients.
基金This study was supported by the National Nature Science Foundation of China[No.81570505]Health Research&Special Projects Grant of China[No.201002020]+1 种基金Ministry of Science and Technology of China[No.2015CB943203]CAMS Innovation Fund for Medical Sciences[No.2016-I2M-3–001].
文摘Background:Matrix Gla protein(MGP)is a secreted protein contributed to the immunomodulatory functions of mesenchymal stromal cells.Microarray profiling found a significantly higher expression level of the extracellular matrix gene MGP in patients with ulcerative colitis(UC).However,little is known about the role of MGP in UC and its upstream signaling regulation.This study aimed to identify the expression of MGP in UC and its upstream regulator mechanism.Methods:Colonicmucosa biopsies were obtained frompatients with UC and healthy controls.DNAmicroarray profiling was used to explore underlying genes correlating with UC development.Mice were fed with water containing different concentrations of dextran sodiumsulfate(DSS)to induce an experimental colitismodel.Colonic tissues were collected and evaluated using immunohistochemistry,immunoblot,real-time polymerase chain reaction,and chromatin immunoprecipitation assay.Bioinformatics analysis was performed to identify candidate MGP gene-promoter sequence and transcription-initiation sites.Luciferase-reporter gene assay was conducted to examine the potential transcription factor ofMGP gene expression.Results:The expression of MGP was significantly increased in colonic tissues from UC patients and DSS-induced colitis models,and was positively correlated with disease severity.Bioinformatics analysis showed a conserved binding site for Egr-1 in the upstream region of human MGP gene.The significantly higher level of Egr-1 gene expression was found in UC patients than in healthy controls.The activity of luciferase was significantly enhanced in the Egr-1 expression plasmid cotransfected group than in the control group and was further inhibited when co-transfected with the Egr-1 binding-site mutated MGP promoter.Conclusions:Up-regulated expression of MGP was found in UC patients and DSS-induced colitis.The expression of MGP can be regulated by Egr-1.
文摘基质GLA蛋白(matrix gla protein MGP)是体内软骨内骨形成和血管内钙化的重要调节因子,是矿盐沉积的重要抑制物。近年来发现绝经后妇女在发生骨质疏松症的同时还常伴有血管的钙化,认为两者可能存在着密切的联系。MGP抑制血管钙化同时与骨代谢密切相关。笔者对MGP与绝经后骨质疏松症的关系进行了简要的综述。
