miR-124 通过靶向 Sp7 调节骨髓间充质干细胞的成骨分化。
miR‑124 regulates the osteogenic differentiation of bone marrow‑derived mesenchymal stem cells by targeting Sp7.
机构信息
Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330031, P.R. China.
Department of Geriatrics, Institute of Aging and Geriatrics, The Second Xiang‑Ya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
出版信息
Mol Med Rep. 2019 May;19(5):3807-3814. doi: 10.3892/mmr.2019.10054. Epub 2019 Mar 18.
MicroRNAs (miRNAs) are novel key regulators of cellular differentiation. miR‑124 has been reported to regulate osteogenic differentiation of bone marrow‑derived mesenchymal stem cells (BMSCs). However, the specific mechanisms involved have not yet been fully elucidated. The present study aimed to investigate the effect of miR‑124 on osteogenic differentiation of BMSCs and its underlying mechanisms. In the present study, it was found that alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion, and the protein levels of osterix (Sp7) and runt‑related transcription factor 2 (Runx2) were significantly increased, whereas the expression of miR‑124 was decreased in a time‑dependent manner during osteogenic differentiation of BMSCs. Following overexpression of miR‑124 via transfection of miR‑124 mimics in BMSCs, Runx2 protein expression and ALP activity were significantly decreased. By contrast, inhibition of miR‑124 expression led to an increase in ALP activity and Runx2 expression. Sp7 expression was suppressed in BMSCs transfected with miR‑124 mimics while increased when miR‑124 expression was inhibited, indicating that miR‑124 regulates the expression of Sp7. Moreover, a luciferase reporter assay further verified that Sp7 is the direct target of miR‑124. Finally, the effect of miR‑124 inhibitor on promoting the differentiation of BMSCs was abolished following treatment with a small interfering RNA targeting Sp7. Taken together, the present study demonstrates that miR‑124 inhibits the osteogenic differentiation of BMSCs by targeting Sp7.
微小 RNA（miRNA）是细胞分化的新型关键调控因子。已有研究报道称，miR-124 可调节骨髓间充质干细胞（BMSC）的成骨分化。然而，其具体的作用机制尚未完全阐明。本研究旨在探讨 miR-124 对 BMSC 成骨分化的影响及其潜在机制。本研究发现，碱性磷酸酶（ALP）活性、骨钙素（OC）分泌以及osterix（Sp7）和 runt 相关转录因子 2（Runx2）的蛋白水平在 BMSC 成骨分化过程中呈时间依赖性升高，而 miR-124 的表达呈下降趋势。在 BMSC 中转染 miR-124 模拟物以过表达 miR-124 后，Runx2 蛋白表达和 ALP 活性明显降低。相反，抑制 miR-124 的表达导致 ALP 活性和 Runx2 表达增加。转染 miR-124 模拟物的 BMSC 中 Sp7 表达受到抑制，而抑制 miR-124 表达则导致 Sp7 表达增加，表明 miR-124 可调节 Sp7 的表达。此外，荧光素酶报告基因检测进一步证实 Sp7 是 miR-124 的直接靶基因。最后，用 Sp7 的小干扰 RNA 处理后，miR-124 抑制剂促进 BMSC 分化的作用被消除。综上所述，本研究表明 miR-124 通过靶向 Sp7 抑制 BMSC 的成骨分化。
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