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成骨诱导相关的激素性股骨头坏死骨髓间充质干细胞的 microRNA 表达谱分析

MicroRNA Expression Profiling of Bone Marrow Mesenchymal Stem Cells in Steroid-Induced Osteonecrosis of the Femoral Head Associated with Osteogenesis.

机构信息

Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, China (mainland).

出版信息

Med Sci Monit. 2018 Mar 28;24:1813-1825. doi: 10.12659/msm.909655.

Abstract

BACKGROUND Steroid-induced osteonecrosis of the femoral head (SONFH) is a common orthopedic disease associated with the application of glucocorticoid (GC). In this study, we detected the microRNAs (miRNAs) differentially expressed in bone marrow mesenchymal stem cells (BMSCs) from SONFH patients, and target gene predictions were performed, and the functions of the target genes was verified. MATERIAL AND METHODS BMSCs collected from patients with SONFH and femoral neck fracture (FNF) constituted the SONFH group (n=3) and FNF (control) group (n=3), respectively. MiRNA microarray analysis was utilized to detect the differentially expressed miRNAs, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the microarray results. The target genes and functions of the differentially expressed miRNAs were analyzed using a bioinformatics database. RESULTS The microarray results revealed that compared with the control group, 22 miRNAs were identified differentially expressed in the SONFH group, with 17 upregulated and 5 downregulated. Further qRT-PCR validation of differentially expressed miRNAs confirmed that hsa-miR-601, hsa-miR-452-3p, hsa-miR-647, and hsa-miR-516b-5p were significantly increased, whereas hsa-miR-122-3p was significantly decreased. During osteogenic differentiation, hsa-miR-601, hsa-miR-452-3p, hsa-miR-647, hsa-miR-516b-5p, and hsa-miR-127-5p were significantly downregulated, whereas hsa-miR-122-3p was significantly upregulated, and miRNAs showed a converse tendency during adipogenic differentiation. CONCLUSIONS Six miRNAs associated with osteogenic and adipogenic differentiation were identified differentially expressed in the BMSCs of SONFH patients; these miRNAs may serve as novel biomarkers or therapeutic targets for SONFH.

摘要

背景

激素诱导性股骨头坏死(SONFH)是一种常见的骨科疾病,与糖皮质激素(GC)的应用有关。在本研究中,我们检测了 SONFH 患者骨髓间充质干细胞(BMSCs)中差异表达的 microRNAs(miRNAs),并进行了靶基因预测,验证了靶基因的功能。

材料和方法

SONFH 组(n=3)和股骨颈骨折(FNF)对照组(n=3)分别采集 SONFH 患者和 FNF 患者的 BMSCs。利用 miRNA 微阵列分析检测差异表达的 miRNAs,并用实时定量聚合酶链反应(qRT-PCR)验证微阵列结果。利用生物信息学数据库分析差异表达 miRNAs 的靶基因和功能。

结果

微阵列结果显示,与对照组相比,SONFH 组有 22 个 miRNAs 差异表达,其中 17 个上调,5 个下调。进一步 qRT-PCR 验证差异表达 miRNAs 证实,hsa-miR-601、hsa-miR-452-3p、hsa-miR-647 和 hsa-miR-516b-5p 明显上调,而 hsa-miR-122-3p 明显下调。在成骨分化过程中,hsa-miR-601、hsa-miR-452-3p、hsa-miR-647、hsa-miR-516b-5p 和 hsa-miR-127-5p 明显下调,而 hsa-miR-122-3p 明显上调,miRNAs 在成脂分化过程中表现出相反的趋势。

结论

在 SONFH 患者的 BMSCs 中,鉴定出 6 个与成骨和成脂分化相关的差异表达 miRNA;这些 miRNA 可能作为 SONFH 的新型生物标志物或治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9971/5887684/8c9d0071ac90/medscimonit-24-1813-g001.jpg

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