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首页> 外文期刊>Journal of Cellular Physiology >TIEG and estrogen modulate SOST expression in the murine skeleton
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TIEG and estrogen modulate SOST expression in the murine skeleton

机译：TIEG和雌激素调节苏斯特表达的小鼠骨骼

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TIEG knockout (KO) mice exhibit a female‐specific osteopenic phenotype and altered expression of TIEG in humans is associated with osteoporosis. Gene expression profiling studies identified sclerostin as one of the most highly up‐regulated transcripts in the long bones of TIEG KO mice relative to WT littermates suggesting that TIEG may regulate SOST expression. TIEG was shown to substantially suppress SOST promoter activity and the regulatory elements through which TIEG functions were identified using promoter deletion and chromatin immunoprecipitation assays. Knockdown of TIEG in IDG‐SW3 osteocyte cells using shRNA and CRISPR‐Cas9 technology resulted in increased SOST expression and delayed mineralization, mimicking the results obtained from TIEG KO mouse bones. Given that TIEG is an estrogen regulated gene, and as changes in the hormonal milieu affect SOST expression, we performed ovariectomy (OVX) and estrogen replacement therapy (ERT) studies in WT and TIEG KO mice followed by miRNA and mRNA sequencing of cortical and trabecular compartments of femurs. SOST expression levels were considerably higher in cortical bone compared to trabecular bone. In cortical bone, SOST expression was increased following OVX only in WT mice and was suppressed following ERT in both genotypes. In contrast, SOST expression in trabecular bone was decreased following OVX and significantly increased following ERT. Interestingly, a number of miRNAs that are predicted to target sclerostin exhibited inverse expression levels in response to OVX and ERT. These data implicate important roles for TIEG and estrogen‐regulated miRNAs in modulating SOST expression in bone.
机译：TIEG淘汰赛(KO)小鼠表现出女性地理osteopenic表型和改变的表达TIEG在人类与骨质疏松症有关。基因表达分析研究确定sclerostin之一最高度的监管长骨头的成绩单TIEG KO小鼠相对于WT同窝出生的暗示TIEG可以调节苏斯特的表达。显著抑制苏斯特和推广活动监管TIEG元素使用子删除功能被确定和染色质免疫沉淀反应化验。击倒的TIEG IDG SW3骨细胞的细胞使用成分和CRISPR Cas9技术了增加苏斯特表达和延迟矿化,模仿获得的结果从TIEG KO小鼠骨骼。雌激素调控基因的变化荷尔蒙环境影响苏斯特表达,我们进行卵巢切除术(OVX)和雌激素替代疗法(ERT)研究在WT和TIEGKO小鼠microrna和信使rna序列紧随其后皮质和股骨的小梁的隔间。苏斯特表达水平是相当高的在皮质骨骨小梁。皮质骨,苏斯特表达增加后只在WT OVX小鼠和镇压后ERT基因型。苏斯特表达在骨小梁减少后OVX和显著增加接受方。预测的目标sclerostin展出逆OVX和表达水平接受方。在调制TIEG和雌激素调节microrna苏斯特表达骨头。

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