MiR-34a Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells via the RBP2/NOTCH1/CYCLIN D1 Coregulatory Network.
MiR-34a Promotes Osteogenic Differentiation of Human Adipose-Derived Stem Cells via the RBP2/NOTCH1/CYCLIN D1 Coregulatory Network.
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MiR-34a 通过 RBP2/NOTCH1/CYCLIN D1 核心调节网络促进人类脂肪干细胞的成骨分化
DOI：
10.1016/j.stemcr.2016.06.010
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发表时间：
2016-08-09
影响因子：
5.9
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Fan C;Jia L;Zheng Y;Jin C;Liu Y;Liu H;Zhou Y
MiR-34 a在人脂肪源性干细胞（hASC）的成骨分化过程中被证实上调。miR-34 a的过表达显著增加了体外培养的hASCs的碱性磷酸酶活性、矿化能力和成骨相关基因的表达。在hASC中过表达miR-34 a后，也观察到体内异位骨形成增强。机制研究表明，miR-34 a抑制视网膜母细胞瘤结合蛋白2（RBP 2）的表达，并降低报告基因构建体的荧光素酶活性，该报告基因构建体在RBP 2的3′ UTR中含有推定的miR-34 a结合位点。此外，miR-34 a通过靶向RBP 2、NOTCH 1和CYCLIN D1下调NOTCH 1和CYCLIN D1的表达，并上调RUNX 2的表达。综上所述，我们的研究结果表明，miR-34 a通过RBP 2/NOTCH 1/CYCLIN D1共调节网络促进hASCs的成骨分化，表明miR-34 a靶向治疗可能是促进骨再生的有价值的方法。MiR-34 a通过RBP 2/NOTCH 1/CYCLIN D1网络促进hASCs的成骨分化在这篇文章中，Zhou及其同事表明miR-34 a在体外和体内促进hASCs的成骨分化。双荧光素酶报告基因检测显示，miR-34 a可直接靶向RBP 2 mRNA，并通过RBP 2/NOTCH 1/CYCLIN D1网络促进hASCs的成骨，提示miR-34 a靶向治疗可能是一种有价值的促进骨再生的方法。
MiR-34a was demonstrated to be upregulated during the osteogenic differentiation of human adipose-derived stem cells (hASCs). Overexpression of miR-34a significantly increased alkaline phosphatase activity, mineralization capacity, and the expression of osteogenesis-associated genes in hASCs in vitro. Enhanced heterotopic bone formation in vivo was also observed upon overexpression of miR-34a in hASCs. Mechanistic investigations revealed that miR-34a inhibited the expression of retinoblastoma binding protein 2 (RBP2) and reduced the luciferase activity of reporter gene construct comprising putative miR-34a binding sites in the 3′ UTR of RBP2. Moreover, miR-34a downregulated the expression of NOTCH1 and CYCLIN D1 and upregulated the expression of RUNX2 by targeting RBP2, NOTCH1, and CYCLIN D1. Taken together, our results suggested that miR-34a promotes the osteogenic differentiation of hASCs via the RBP2/NOTCH1/CYCLIN D1 coregulatory network, indicating that miR-34a-targeted therapy could be a valuable approach to promote bone regeneration. MiR-34a promotes osteogenesis of hASCs in vitro and in vivo MiR-34a directly binds to the 3′ UTR of RBP2 mRNA in hASCs MiR-34a promotes osteogenesis of hASCs via the RBP2/NOTCH1/CYCLIN D1 network In this article, Zhou and colleagues show that miR-34a promotes the osteogenic differentiation of hASCs in vitro and in vivo. Dual-luciferase reporter assay demonstrated that miR-34a directly targets RBP2 mRNA and promotes osteogenesis of hASCs via the RBP2/NOTCH1/CYCLIN D1 network, indicating that miR-34a-targeted therapy could be a valuable approach to promote bone regeneration.