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微小 RNA-23a-5p 通过靶向丝裂原活化蛋白激酶 13 调节人骨髓间充质干细胞的成骨分化。

MicroRNA-23a-5p regulates osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting mitogen-activated protein kinase-13.

机构信息

Department of Stomatology, Tianjin First Central Hospital, Nankai, Tianjin 300382, P.R. China.

出版信息

Mol Med Rep. 2018 Mar;17(3):4554-4560. doi: 10.3892/mmr.2018.8452. Epub 2018 Jan 18.

DOI:10.3892/mmr.2018.8452
PMID:29344643
Abstract

The molecular mechanisms of osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) remain to be fully elucidated. MicroRNAs (miRs) serve vital roles in the process of regulating osteogenic differentiation of BMSCs. The present study aimed to investigate the role of miR‑23a‑5p in osteogenic differentiation of human (h)BMSCs, and the underlying molecular mechanism. The results of reverse transcription‑quantitative polymerase chain reaction demonstrated that miR‑23a‑5p was significantly downregulated in the process of osteogenic differentiation. Upregulation of miR‑23a‑5p inhibited osteogenic differentiation of hBMSCs, and down‑regulated expression of miR‑23a‑5p enhanced this process, which was confirmed by alkaline phosphatase (ALP) and Alizarin Red S staining. A dual‑luciferase reporter assay confirmed that mitogen‑activated protein kinase 13 (MAPK13) was a direct target of miR‑23a‑5p. In addition, knockdown of MAPK13 inhibited osteogenic differentiation of hBMSCs, similar to the effect of upregulation of miR‑23a‑5p. Finally, the knockdown of MAPK13 also blocked the effect of miR‑23a‑5p in osteogenic differentiation of hBMSCs, which was also confirmed by ALP and Alizarin Red S staining. These results indicated that by targeting MAPK13, miR‑23a‑5p serves a vital role in osteogenic differentiation of hBMSCs, which may provide novel clinical treatments for bone injury however, further studies are required.

摘要

骨髓间充质干细胞(BMSCs)成骨分化的分子机制仍有待充分阐明。微小 RNA(miRNA/miR)在调节 BMSCs 成骨分化的过程中发挥着重要作用。本研究旨在探讨 miR-23a-5p 在人(h)BMSCs 成骨分化中的作用及其潜在的分子机制。逆转录-定量聚合酶链反应的结果表明,miR-23a-5p 在成骨分化过程中显著下调。miR-23a-5p 的上调抑制 hBMSCs 的成骨分化,而下调 miR-23a-5p 的表达则增强了这一过程,碱性磷酸酶(ALP)和茜素红 S 染色证实了这一点。双荧光素酶报告基因检测证实丝裂原活化蛋白激酶 13(MAPK13)是 miR-23a-5p 的直接靶基因。此外,MAPK13 的敲低抑制了 hBMSCs 的成骨分化,这与上调 miR-23a-5p 的效果相似。最后,MAPK13 的敲低也阻断了 miR-23a-5p 在 hBMSCs 成骨分化中的作用,这也通过 ALP 和茜素红 S 染色得到了证实。这些结果表明,通过靶向 MAPK13,miR-23a-5p 在 hBMSCs 的成骨分化中发挥着重要作用,这可能为骨损伤的临床治疗提供新的方法,但还需要进一步的研究。

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