Suppr超能文献

微小 RNA-186-5p 通过靶向非创伤性骨坏死中的 CXCL13 来调节成骨细胞分化和细胞活力。

MicroRNA‑186‑5p mediates osteoblastic differentiation and cell viability by targeting CXCL13 in non‑traumatic osteonecrosis.

机构信息

Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Cancer Centre, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

出版信息

Mol Med Rep. 2019 Nov;20(5):4594-4602. doi: 10.3892/mmr.2019.10710. Epub 2019 Sep 26.

Abstract

MicroRNAs (miRs) serve varying and important roles in the pathogenesis of non‑traumatic osteonecrosis (ON). However, the role miR‑186‑5p serves in the pathogenesis of osteonecrosis remains unknown and the clinical outcome of ON is still uncertain. The aim of the present study was to determine the expression characteristics, biological function and molecular mechanisms of miR‑186‑5p, which is associated with cancer development and progression, in osteoblastic differentiation and cell viability. The results of the present study showed that the expression levels of miR‑186‑5p were significantly higher in clinical non‑traumatic ON compared with osteoarthritis samples (P=0.0001). An inverse association was observed between miR‑186‑5p and CXCL13 expression levels. Furthermore, miR‑186‑5p inhibited phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling, downregulated osteoblast‑specific markers and reduced the viability and differentiation of human mesenchymal stem cells from bone marrow (HMSC‑bm) through targeting CXCL13. Increasing expression of CXCL13 in HMSC‑bm cells partially restored miR‑186‑5p‑mediated inhibition. In conclusion, abrogation of PI3K/AKT signaling triggered by miR‑186‑5p/CXCL13 may contribute to ON pathogenesis. These results highlight the possible clinical value of miR‑186‑5p in treatment for non‑traumatic ON.

摘要

微小 RNA(miRs)在非创伤性骨坏死(ON)的发病机制中发挥着不同且重要的作用。然而,miR-186-5p 在骨坏死发病机制中的作用尚不清楚,ON 的临床结局仍然不确定。本研究旨在确定与癌症发展和进展相关的微小 RNA-186-5p 的表达特征、生物学功能和分子机制,在成骨细胞分化和细胞活力中。本研究结果表明,miR-186-5p 的表达水平在临床非创伤性 ON 与骨关节炎样本相比明显更高(P=0.0001)。miR-186-5p 与 CXCL13 表达水平呈负相关。此外,miR-186-5p 通过靶向 CXCL13 抑制磷酸肌醇 3 激酶(PI3K)/蛋白激酶 B(AKT)信号通路,下调成骨细胞特异性标志物,降低骨髓间充质干细胞(HMSC-bm)的活力和分化。增加 CXCL13 在 HMSC-bm 细胞中的表达部分恢复了 miR-186-5p 介导的抑制作用。综上所述,PI3K/AKT 信号通路的阻断可能是由 miR-186-5p/CXCL13 引起的,这可能有助于 ON 的发病机制。这些结果突出了 miR-186-5p 在非创伤性 ON 治疗中的潜在临床价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27e3/6797973/6af77cdfb034/MMR-20-05-4594-g00.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验