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Melatonin‐mediated miR‐526b‐3p and miR‐590‐5p upregulation promotes chondrogenic differentiation of human mesenchymal stem cells
Authors:Zizhao Wu  Xianjian Qiu  Bo Gao  Chengjie Lian  Yan Peng  Anjing Liang  Caixia Xu  Wenjie Gao  Liangming Zhang  Peiqiang Su  Limin Rong  Dongsheng Huang
Affiliation:1. Department of Orthopedics, Sun Yat‐sen Memorial Hospital of Sun Yat‐sen University, Guangzhou, Guangdong, China;2. Department of Orthopedics, The First Affiliated Hospital of Sun Yat‐sen University, Guangzhou, Guangdong, China;3. Research Centre for Translational Medicine, The First Affiliated Hospital of Sun Yat‐sen University, Guangzhou, Guangdong, China;4. Department of Spine Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University, Xi'an, China;5. Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat‐Sen University, Guangzhou, China;6. Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, The First Affiliated Hospital of Sun Yat‐sen University, Guangzhou, Guangdong, China
Abstract: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.
Keywords:chondrogenesis  human mesenchymal stem cells  melatonin  miR‐526b‐3p  miR‐590‐5p  SMAD7
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