Melatonin‐mediated miR‐526b‐3p and miR‐590‐5p upregulation promotes chondrogenic differentiation of human mesenchymal stem cells
Melatonin‐mediated miR‐526b‐3p and miR‐590‐5p upregulation promotes chondrogenic differentiation of human mesenchymal stem cells
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DOI：
10.1111/jpi.12483
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发表时间：
2018-08
影响因子：
10.3
通讯作者：
Zizhao Wu;X. Qiu;Bo Gao;Chengjie Lian;Yan Peng;Anjing Liang;Caixia Xu;Wenjie Gao;Liangming Zhang
中科院分区：
文献类型：
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作者：
Zizhao Wu;X. Qiu;Bo Gao;Chengjie Lian;Yan Peng;Anjing Liang;Caixia Xu;Wenjie Gao;Liangming Zhang
骨髓间充质干细胞(BMSCs)具有内在的软骨分化潜能，非常适合用于软骨再生的治疗。越来越多的证据表明，褪黑素可以促进人骨髓间充质干细胞向软骨细胞分化。然而，人们对这种机制知之甚少。MicroRNAs(MiRNAs)已被证明对BMSCs的分化起调控作用，但它们在褪黑素促进的软骨分化中的作用尚不清楚。在这里，我们证明褪黑素通过上调miR-526b-3p和miR-590-5p促进人BMSCs向软骨方向分化。在机制上，升高的miR-526b-3p和miR-590-5p通过靶向Smad7而增强Smad1的磷酸化。此外，应用miR-526b-3p模拟物或miR-590-5p模拟物成功地促进了人BMSCs的软骨分化。总之，我们的研究表明，使用褪黑素或miRNA转导修饰BMSCs可能是治疗软骨损伤和退变的有效方法。
Bone marrow‐derived mesenchymal stem cells (BMSCs), with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. Accumulating evidence has demonstrated that melatonin can promote chondrogenic differentiation in human BMSCs. However, little is known about the mechanism. MicroRNAs (miRNAs) have been shown to regulate the differentiation of BMSCs, but their roles in melatonin‐promoted chondrogenic differentiation have not been characterized. Here, we demonstrate that melatonin promoted chondrogenic differentiation of human BMSCs via upregulation of miR‐526b‐3p and miR‐590‐5p. Mechanistically, the elevated miR‐526b‐3p and miR‐590‐5p enhanced SMAD1 phosphorylation by targeting SMAD7. Additionally, administration of miR‐526b‐3p mimics or miR‐590‐5p mimics successfully promoted the chondrogenic differentiation of human BMSCs. Collectively, our study suggests that modification of BMSCs using melatonin or miRNA transduction could be an effective therapy for cartilage damage and degeneration.