MiR-210-3p inhibits osteogenic differentiation and promotes adipogenic differentiation correlated with Wnt signaling in ERα-deficient rBMSCs
MiR-210-3p inhibits osteogenic differentiation and promotes adipogenic differentiation correlated with Wnt signaling in ERα-deficient rBMSCs
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DOI：
10.1002/jcp.28916
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Yang, Li
中科院分区：
文献类型：
--
作者：
Li, Xiaoyun;Peng, Bojia;Yang, Li
MicroRNAs （miRNAs）通过多种信号通路调控生物体内的活动，在骨质疏松症的发生发展中发挥重要作用。骨髓间充质干细胞成骨与成脂分化的平衡与骨质疏松症的发生密切相关。内质网α调节各种组织的骨代谢。然而，内质网α、mirna与rBMSCs分化之间的相关性尚不清楚。在本研究中，我们使用慢病毒转染rBMSCs构建ER α缺陷模型，分析对照组和ER α缺陷rBMSCs之间表达mirna的差异。结果显示，25个mirna表达上调，164个mirna表达下调，其中一些mirna如miR-210-3p和miR-214-3p与成骨或脂肪分化有关，并与特定的信号通路有关。接下来，我们过表达miR-210-3p来评估其对rBMSCs成骨和成脂分化的影响，并确定miR-210-3p、Wnt信号通路与rBMSCs分化之间的关系。结果表明，ER α缺乏抑制成骨分化，促进成脂分化，并调节部分mirna的表达。同时，miR-210-3p的过表达促进了rBMSCs的成骨分化，抑制了rBMSCs的成脂分化，这一过程可能与Wnt信号通路有关。总之，我们在ER α缺失的rBMSCs中发现了一组上调和下调的mirna，它们可能在调节成骨或成脂分化中发挥重要作用。其中，miR-210-3p在ER α缺失的rBMSCs中抑制成骨分化并促进与Wnt信号通路相关的成脂分化，为骨代谢调控提供了新的见解。
MicroRNAs (miRNAs) regulate activities in living organisms through various signaling pathways and play important roles in the development and progression of osteoporosis. The balance between osteogenic and adipogenic differentiation of rBMSCs is closely related to the occurrence of osteoporosis. ER alpha regulates bone metabolism in various tissues. However, the correlation among ER alpha, miRNAs, and the differentiation of rBMSCs is still unclear. In this study, we used lentivirus transfection into rBMSCs to construct an ER alpha-deficient model, analyzed the differences in expressed miRNAs between control and ER alpha-deficient rBMSCs. The results revealed that the expression of 25 miRNAs were upregulated, 164 miRNAs were downregulated, and some of the regulated miRNAs such as miR-210-3p and miR-214-3p were related to osteogenic or adipogenic differentiation, as well as to particular signaling pathways. Next, we overexpressed miR-210-3p to evaluate its effects on the osteogenic and adipogenic differentiation of rBMSCs, and identified the relationship among miR-210-3p, Wnt signaling pathway, and the differentiation of rBMSCs. The results indicated that ER alpha-deficient inhibited osteogenic differentiation, promoted adipogenic differentiation, and regulated the expression of some miRNAs. Meanwhile, overexpression of miR-210-3p promoted osteogenic differentiation and inhibited adipogenic differentiation of rBMSCs, processes likely to be related to the Wnt signaling pathway. In conclusion, we identified a group of upregulated and downregulated miRNAs in ER alpha-deficient rBMSCs that might play a vital role in regulating osteogenic or adipogenic differentiation. One of these, miR-210-3p, inhibited osteogenic differentiation and promoted adipogenic differentiation correlated with the Wnt signaling pathway in ER alpha-deficient rBMSCs, providing new insight into the regulation of bone metabolism.