Li Yuan, Yang Fan, Gao Manqi, Gong Rui, Jin Mengyu, Liu Tianyi, Sun Yi, Fu Yutuo, Huang Qi, Zhang Wenwen, Liu Shenzhen, Yu Meixi, Yan Gege, Feng Chao, He Mingyu, Zhang Lai, Ding Fengzhi, Ma Wenya, Bi Zhenggang, Xu Chaoqian, Yuan Ye, Cai Benzhi, Yang Lei
Department of Pharmacology, The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China.
Department of Pharmacology, The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China; College of Pharmacy, University of Cincinnati, Cincinnati, OH 45220, USA.
Mol Ther Nucleic Acids. 2019 Sep 6;17:590-600. doi: 10.1016/j.omtn.2019.06.023. Epub 2019 Jul 11.
Bone marrow-derived mesenchymal stem cells (BMSCs) have been suggested to possess the capacity to differentiate into different cell lineages. Maintaining a balanced stem cell differentiation program is crucial to the bone microenvironment and bone development. MicroRNAs (miRNAs) have played a critical role in regulating the differentiation of BMSCs into particular lineage. However, the role of miR-149-3p in the adipogenic and osteogenic differentiation of BMSCs has not been extensively discovered. In this study, we aimed to detect the expression levels of miR-149-3p during the differentiation of BMSCs and investigate whether miR-149-3p participated in the lineage choice of BMSCs or not. Compared with mimic-negative control (NC), miR-149-3p mimic decreased the adipogenic differentiation potential of BMSCs and increased the osteogenic differentiation potential. Further analysis revealed that overexpression of miR-149-3p repressed the expression of fat mass and obesity-associated (FTO) gene through binding to the 3' UTR of the FTO mRNA. Also, the role of miR-149-3p mimic in inhibiting adipogenic lineage differentiation and potentiating osteogenic lineage differentiation was mainly through targeting FTO, which also played an important role in regulating body weight and fat mass. In addition, BMSCs treated with miR-149-3p anti-miRNA oligonucleotide (AMO) exhibited higher potential to differentiate into adipocytes and lower tendency to differentiate into osteoblasts compared with BMSCs transfected with NC. In summary, our results detected the effects of miR-149-3p in cell fate specification of BMSCs and revealed that miR-149-3p inhibited the adipogenic differentiation of BMSCs via a miR-149-3p/FTO regulatory axis. This study provided cellular and molecular insights into the observation that miR-149-3p was a prospective candidate gene for BMSC-based bone tissue engineering in treating osteoporosis.
骨髓间充质干细胞（BMSCs）被认为具有分化为不同细胞谱系的能力。维持平衡的干细胞分化程序对骨微环境和骨发育至关重要。微小RNA（miRNAs）在调节BMSCs向特定谱系分化中发挥了关键作用。然而，miR-149-3p在BMSCs成脂和成骨分化中的作用尚未被广泛发现。在本研究中，我们旨在检测BMSCs分化过程中miR-149-3p的表达水平，并研究miR-149-3p是否参与BMSCs的谱系选择。与模拟阴性对照（NC）相比，miR-149-3p模拟物降低了BMSCs的成脂分化潜能，增加了成骨分化潜能。进一步分析表明，miR-149-3p的过表达通过与FTO mRNA的3'UTR结合抑制脂肪量和肥胖相关（FTO）基因的表达。此外，miR-149-3p模拟物在抑制成脂谱系分化和增强成骨谱系分化中的作用主要是通过靶向FTO，FTO在调节体重和脂肪量方面也起着重要作用。此外，与转染NC的BMSCs相比，用miR-149-3p抗miRNA寡核苷酸（AMO）处理的BMSCs表现出更高的分化为脂肪细胞的潜能和更低的分化为成骨细胞的倾向。总之，我们的结果检测了miR-149-3p在BMSCs细胞命运决定中的作用，并揭示miR-1
