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.

中文翻译：

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褪黑素介导的miR-526b-3p和miR-590-5p上调促进人间充质干细胞的软骨分化

具有固有软骨分化潜能的骨髓源间充质干细胞（BMSC）似乎非常适合用于软骨再生的治疗用途。越来越多的证据表明褪黑激素可以促进人骨髓间充质干细胞的软骨形成分化。但是，对该机制知之甚少。MicroRNA（miRNA）已被证明可调节BMSC的分化，但尚未阐明它们在褪黑激素促进的软骨形成分化中的作用。在这里，我们证明了褪黑素通过上调miR-526b-3p和miR-590-5p促进人BMSC的软骨形成分化。从机制上讲，升高的miR-526b-3p和miR-590-5p通过靶向SMAD7增强了SMAD1磷酸化。此外，miR-526b-3p模仿物或miR-590-5p模仿物的施用成功促进了人BMSC的软骨分化。总体而言，我们的研究表明，使用褪黑激素或miRNA转导修饰BMSCs可能是治疗软骨损伤和变性的有效方法。