Huang Mengqi, Qing Ying, Shi Qi, Cao Yingguang, Song Ke
Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Biochem Biophys Res Commun. 2017 Sep 23;491(3):571-577. doi: 10.1016/j.bbrc.2017.07.163. Epub 2017 Jul 29.
Human umbilical mesenchymal stem cells (UCMSCs) have been wildly used in tissue engineering field as a promising source because of their unlimited and noninvasive origin. To selectively induce osteogenic differentiation of UCMSCs, it's imperative to understand the regulatory molecular mechanism underlying the process of how these cells switch into osteogenic lineage path. We previously showed enhanced sonic hedgehog (Shh) signaling pathway upon osteogenic induction in mesenchymal stem cells. In this study, miRNA-seq analysis revealed substantial Shh-dependent expression of distinct miRNAs, including miR-342-3p, during ostogenesis. RT-qPCR confirmed that miR-342-3p was increased at a greater level when Shh signaling pathway was activated by N-terminal of Shh ligand compared with osteogenic induction alone, in contrast to the decreasing of suppressor-of-fused protein (Sufu). Consistently, transient overexpressing miR342-3p in UCMSCs via miR-342-3p mimics dramatically decreased Sufu, a suppressor of Gli, while osteogenic markers, including alkaline phosphate and osteocalcin, were upregulated during osteogenic induction, indicating that miR-342-3p might be involved in osteogenesis through the Shh signaling pathway. In conclusion, this study showed the potential of miR-342-3p as a therapeutic target to promote bone regeneration by modulating expression of Sufu in UCMSCs.
人脐间充质干细胞(UCMSCs)因其来源无限且无创,已作为一种有前景的来源在组织工程领域得到广泛应用。为了选择性诱导UCMSCs向成骨分化,了解这些细胞如何转变为成骨谱系途径过程中的调控分子机制至关重要。我们之前发现间充质干细胞在成骨诱导后 Sonic hedgehog(Shh)信号通路增强。在本研究中,miRNA测序分析显示在成骨过程中,包括miR-342-3p在内的多种不同miRNA存在大量依赖Shh的表达。逆转录定量聚合酶链反应(RT-qPCR)证实,与单独成骨诱导相比,当Shh信号通路被Shh配体的N端激活时,miR-342-3p的表达水平升高幅度更大,而融合抑制蛋白(Sufu)则减少。同样,通过miR-342-3p模拟物在UCMSCs中瞬时过表达miR-342-3p可显著降低Gli的抑制因子Sufu,而成骨诱导过程中成骨标志物(包括碱性磷酸酶和骨钙素)上调,这表明miR-342-3p可能通过Shh信号通路参与成骨过程。总之,本研究表明miR-342-3p有潜力作为治疗靶点,通过调节UCMSCs中Sufu的表达来促进骨再生。