基于骨组织Runx2、Osterix启动子甲基化探究鹿茸中药复方对去卵巢骨质疏松症大鼠的疗效机制

Exploring Therapeutic Mechanism of Pilose Antler Chinese Herbal Compound on Ovariectomy Osteoporosis Rats Based on Methylation of Runx2 and Osterix Promoter in Bone Tissues

目的基于骨组织Runx2、Osterix启动子甲基化水平,探究鹿茸中药复方对去卵巢骨质疏松症大鼠的疗效机制。方法去卵巢复制绝经后骨质疏松症(Postmenopausal Osteoporosis,PMOP)大鼠模型,将其分4组,分别为:正常组、模型组、鹿茸中药复方组、仙灵骨葆阳性对照组。灌胃14周后,X射线吸收测量法检测骨密度、质谱法检测Runx2、Osterix启动子甲基化水平。结果(1)与正常组比较,模型组第1~6腰椎骨密度明显降低(P<0.01);骨组织Runx2启动子-955 bp^-456 bp CpG1、CpG2甲基化水平明显升高(P<0.05);骨组织Osterix启动子-1082 bp^-583 bp CpG1、CpG2甲基化水平明显升高(P<0.01)。(2)与模型组比较,鹿茸中药复方组、仙灵骨葆阳性对照组第1~6腰椎骨密度明显升高(P<0.05);鹿茸中药复方组骨组织Runx2启动子-955 bp^-456 bp CpG1、CpG3甲基化水平明显降低(P<0.05),Osterix启动子-1082 bp^-583bp CpG1甲基化水平明显降低(P<0.05);仙灵骨葆阳性对照组骨组织Runx2启动子-955 bp^-456 bp CpG1、CpG2甲基化水平明显降低(P<0.05),Osterix启动子-1082 bp^-583 bp CpG1、CpG2甲基化水平明显降低(P<0.01)。结论鹿茸中药复方通过降低骨组织Runx2、Osterix启动子甲基化水平的表观遗传学机制,有效防治PMOP。

Objective To explore the therapeutic mechanism of pilose antler Chinese herbal compound on ovariectomy osteoporosis rats based on methylation level of Runx2 and Osterix promoter in bone tissues.Methods Postmenopausal osteoporosis(PMOP)rat models were established by ovariectomy.All the rats were divided into normal group,model group,pilose antler Chinese herbal compound group and XIANLINGGUBAO positive control group.We detected bone mineral density by X-ray absorptiometry and Runx2 and Osterix promoter methylation level by Mass ARRAY after 14 weeks of gavage.Results①Compared with normal group,lumbar vertebra 1~6 bone mineral density of model group decreased significantly(P<0.01);Runx2 promoter-955 bp-456 bp CpG1 and CpG2 methylation level increased significantly in bone tissues(P<0.05);Osterix promoter-1082 bp-583 bp CpGl and CpG2 methylation level increased significantly in bone tissues(P<0.01).②Compared with model group,lumbar vertebra 1~6 bone mineral density of pilose antler Chinese herbal compound group and XIANLINGGUBAO positive control group increased significantly(P<0.05);Runx2 promoter-955 bp-456 bp CpGl and CpG3 methylation level of pilose antler Chinese herbal compound group decreased significantly in bone tissues(P<0.05),Osterix promoter-1082 bp^-583 bp CpC1 mlethylation level decreased significantly in bone tissues(P<0.05);Runx2 promoter-955 bp-456 bp CpC1 and CpG2 methylation level of XIANLINGGUBAO positive control group decreased significantly in bone tissues(P<0.05),Osterix promoter-1082 bp^-583 bp CpGl and CpG2 methylation level decreased significantly in bone tissues(P<0.01).Conclusions Pilose antler Chinese herbal compound can prevent and cure PMOP effectively by the epigenetic mechanism of reducing Runx2 and Osterix promoter methylation level in bone tissues.