骨硬素启动子甲基化与儿童糖皮质激素性骨质疏松症的相关性研究  

Correlation between methylation of SOST promoter and glucocorticoid-induced osteoporosis in children

作　　者：胡欣 陈礼娟 谭若锟[2] 熊昕[2] Hu Xin;Chen Lijuan;Tan Ruokun;Xiong Xin(Department of Stomatology,the Third People’s Hospital of Chenzhou,Chenzhou 423000,China;Children’s Hospital,North Hospital of the First People’s Hospital of Chenzhou,Chenzhou 423000,China)

机构地区：[1]湖南省郴州市第三人民医院口腔科,郴州423000 [2]湖南省郴州市第一人民医院北院儿童医院新生儿,郴州423000

出　　处：《中华内分泌外科杂志（中英文）》2024年第5期712-718,共7页Chinese Journal of Endocrine Surgery

基　　金：湖南省卫生厅课题基金资助(B2005172)。

摘　　要：目的探究骨硬素(sclerostin,SOST)启动子甲基化与儿童糖皮质激素性骨质疏松症(glucocorticoid induce-dosteoporosis,GIOP)的相关性。方法选择湖南省郴州市第一人民医院北院儿童医院收治的儿童GIOP的患者(66例)作为观察组,同时选择应用糖皮质激素治疗但骨量处于正常范围的患儿作为对照组(72例),对比所有患儿的一般资料,并通过腰椎定量计算机断层扫描(quantitative computed tomography,QCT)对计算机断层扫描(computed tomography,CT)采集的数据处理进行骨密度检测,通过生化分析仪检测骨代谢相关指标的水平;通过荧光定量PCR检测SOST的mRNA表达,酶联免疫吸附法(ELISA)检测SOST蛋白含量的表达;通过甲基化特异聚合酶链反应(methylation specific polymerase chain reaction,MSP)检测SOST基因启动子甲基化状态,对比并分析影响GIOP的危险因素并评估各指标对GIOP患儿的诊疗价值。结果与对照组相比,观察组中儿童的激素应用时间与激素当前剂量的水平均较高,同时其骨代谢指标β-胶原降解产物(β-collagen degradation product,β-CTX)(t=9.87,P<0.01)、I型胶原氨基端延长肽(typeⅠprocollagenamino-terminal peptide,P1NP)(t=16.09,P<0.001)、骨桥蛋白(osteopontin,OPN)(t=21.32,P<0.001)、N端骨钙素(N-MID)(t=15.21,P<0.01)表达水平显著升高,差异有统计学意义;而在骨密度方面,观察组患儿的相关水平较低(t=22.49,P<0.001),同时其SOST mRNA(t=9.48,P<0.01)及蛋白含量(t=7.70,P<0.01)的表达显著下调,且观察组患儿SOST呈现甲基化状态。Pearson分析结果显示,观察组患儿血清SOST蛋白含量水平与β-CTX(r=-0.16,P=0.012)、P1NP(r=-0.35,P=0.021)、OPN(r=-0.25,P=0.043)、N-MID(r=-0.09,P=0.036)水平呈现负相关性,同时由Logistic回归分析可知P1NP(SE=0.35,P<0.001)、OPN(SE=0.37,P<0.001)和SOST(SE=0.33,P<0.001)高表达是影响儿童GIOP发生的危险因素,受试者工作特征曲线(ROC)结果显示SOST的曲线下面积为0.874(95%CI:0.824~0.934),灵敏ObjectiveTo explore the correlation between the methylation of sclerostin(SOST)promoter and glucocorticoid-induced osteoporosis(GIOP)in children.MethodsChildren with GIOP(n=66)were selected as the experimental group.At the same time,children treated with glucocorticoid whose bone mass were selected as the control group(n=72).The general clinical information of all children was compared,and the data collected by CT were detected by lumbar QCT,and the levels of bone metabolism related indexes were detected by biochemical analyzer.The mRNA expression of SOST was detected by fluorescence quantitative PCR,and the protein content of SOST was detected by enzyme-linked Immunosorbent Assay(ELISA).Methylation status of SOST gene promoter was detected by methylation-specific PCR(MSP),and the risk factors affecting GIOP were compared and analyzed,and the diagnostic and therapeutic value of each index for children with GIOP was evaluated.ResultsCompared with the control group,the duration of hormone application and the current dose of hormone in the experimental group were higher,and the expression levels of bone metabolism indexesβ-collagen carboxy terminal peptide(β-CTX)(t=9.87,P<0.01),typeⅠprocollagenamino-terminal peptide(P1NP)(t=16.09,P<0.001),osteopontin(OPN)(t=21.32,P<0.001)and N-MID(t=15.21,P<0.01)were significantly increased,with statistical significance.However,in terms of bone mineral density,the related level of children in the experimental group was low(t=22.49,P<0.001),and the expression of SOST mRNA(t=9.48,P<0.01)and protein content(t=7.70,P<0.01)was significantly decreased,and the children in the experimental group showed methylation status of SOST.Pearson analysis showed that the level of serum SOST protein in the experimental group was negatively correlated with the levels ofβ-CTX(r=-0.16,P=0.012),P1NP(r=-0.35,P=0.021),OPN(r=-0.25,P=0.043)and N-MID(r=-0.09,P=0.036).At the same time,the Logistic regression analysis showed that the high expression of P1NP(SE=0.35,P<0.001),OPN(S E=0.37,P<0.001)and SOST(SE=

关 键 词：骨硬素启动子 甲基化状态 骨密度检测 骨代谢指标 腰椎定量计算机断层扫描 糖皮质激素性骨质疏松症 

分 类 号：R725.8[医药卫生—儿科]