miR-483-3p regulates osteogenic differentiation of bone marrow mesenchymal stem cells by targeting STAT1
miR-483-3p regulates osteogenic differentiation of bone marrow mesenchymal stem cells by targeting STAT1
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miR-483-3p通过靶向STAT1调节骨髓间充质干细胞的成骨分化
DOI：
10.3892/mmr.2019.10700
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发表时间：
2019
影响因子：
3.4
通讯作者：
Xiao Wen Feng
中科院分区：
文献类型：
--
作者：
Xiao Ye;Guo Qi;Jiang Tie Jian;Yuan Ying;Yang Li;Wang Guang Wei;Xiao Wen Feng
骨髓间充质干细胞（BMSCs）的成骨分化受多种细胞内调节因子的调控，包括osterix、RUNX 2、骨形态发生蛋白和转化生长因子β。最近的研究表明，microRNAs（miRs）在这一过程中起着至关重要的作用。在本研究中，miR-483- 3 p水平在小鼠和人BMSC的成骨分化过程中显著增加。miR-483- 3 p的过表达促进成骨分化，而miR-483- 3 p的抑制逆转了这些作用。miR-483- 3 p通过靶向STAT 1调控BMSCs的成骨分化，从而增强RUNX 2的转录活性和核转位。在体内，使用BMSC特异性适体递送系统过表达miR-483- 3 p刺激老年小鼠的骨形成。因此，本研究表明，miR-483- 3 p通过靶向STAT 1促进BMSCs的成骨分化，miR-483-3为年龄相关性骨丢失的潜在治疗靶点。
Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is regulated by a variety of intracellular regulatory factors including osterix, runt-related transcription factor 2 (RUNX2), bone morphogenetic proteins and transforming growth factorβ. Recent studies have shown that microRNAs (miRs) serve a crucial role in this process. In the present study, miR-483-3p levels were significantly increased during osteogenic differentiation of mouse and human BMSCs. Overexpression of miR-483-3p promoted osteogenic differentiation, whereas inhibition of miR-483-3p reversed these effects. miR-483-3p regulated osteogenic differentiation of BMSCs by targeting STAT1, and thus enhancing RUNX2 transcriptional activity and RUNX2 nuclear translocation. In vivo, overexpression of miR-483-3p using a BMSC-specific aptamer delivery system stimulated bone formation in aged mice. Therefore, the present study suggested that miR-483-3p promoted osteogenic differentiation of BMSCs by targeting STAT1, and miR-483-3 prepresent a potential therapeutic target for age-related bone loss.