MicroRNA-664a-5p promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by directly downregulating HMGA2.
MicroRNA-664a-5p promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by directly downregulating HMGA2.
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DOI：
10.1016/j.bbrc.2019.09.122
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发表时间：
2019
影响因子：
3.1
通讯作者：
Yan Zhang;Yue Liu;Ming Wu;Hongyan Wang;Liang Wu;Bo Xu;Wenchao Zhou;Xin-bing Fan;Jin Shao;Tieyi Yang
中科院分区：
文献类型：
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作者：
Yan Zhang;Yue Liu;Ming Wu;Hongyan Wang;Liang Wu;Bo Xu;Wenchao Zhou;Xin-bing Fan;Jin Shao;Tieyi Yang
人骨髓间充质干细胞(BMSCs)的成骨分化一直被认为是骨折愈合的核心问题。MicroRNAs(miRNAs，miRs)参与骨髓间充质干细胞向成骨细胞分化等多种生理过程。在本研究中，我们发现miR-664a-5p在人BMSCs成骨分化过程中表达上调，并且这种上调与成骨相关转录因子2(RUNX2)、碱性磷酸酶(ALP)和骨钙素(OCN)的表达呈正相关。MiR-664a-5p的过表达促进了BMSCs的成骨分化，而miR-664a-5p的过表达则抑制了其成骨分化。此外，高迁移率族A2(HMGA2)mRNA被确定为miR-664a-5p的直接靶标，介导该miRNA的功能。HMGA2过表达可明显抑制miR-664a-5p诱导的BMSCs成骨分化。因此，新近发现的miR-664a-5p-HMGA2通路扩大了我们对人骨髓间充质干细胞成骨分化机制的理解，可能对这种分化的调控提供更深入的见解，并可能为治疗骨质疏松症提供新的有效方法。
Osteogenic differentiation of human bone marrow–derived mesenchymal stem cells (BMSCs) has been regarded as a central issue in fracture healing. MicroRNAs (miRNAs, miRs) participate in diverse physiological processes such as osteoblastic differentiation of BMSCs. In this study, we found that miR-664a-5p was upregulated during osteogenic differentiation of human BMSCs, and this upregulation positively correlated with the expression of osteogenic genes Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteocalcin (OCN). Overexpression of miR-664a-5p promoted the osteogenic differentiation of BMSCs, whereas a knockdown of miR-664a-5p suppressed it. Additionally, high-mobility group A2 (HMGA2) mRNA was identified as a direct target of miR-664a-5p that mediates the function of this miRNA. Overexpression of HMGA2 obviously attenuated miR-664a-5p–induced osteogenic differentiation of BMSCs. Thus, the newly identified miR-664a-5p–HMGA2 pathway expands our understanding of the mechanisms underlying the osteogenic differentiation of human BMSCs, may provide deeper insights into the regulation of this differentiation, and can point to new effective methods for treating osteoporosis.