Identification of differentially expressed microRNAs in knee anterior cruciate ligament tissues surgically removed from patients with osteoarthritis.

Identification of differentially expressed microRNAs in knee anterior cruciate ligament tissues surgically removed from patients with osteoarthritis.
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DOI:
10.3892/ijmm.2017.3086
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发表时间:
2017-10
影响因子:
5.4
通讯作者:
Wen Y
Wen Y
中科院分区:
医学3区
文献类型:
--
作者:
Li B;Bai L;Shen P;Sun Y;Chen Z;Wen Y

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在退行性关节疾病如骨关节炎(OA)中经常观察到交叉韧带的退化。本研究旨在鉴定OA患者和健康受试者(非OA)膝关节前交叉韧带(ACL)组织中差异表达的microRNA(miRNAs或miRs)。通过使用AffyRmiRNA4.0微阵列,共发现22种miRNAs(包括let-7 f-5 p、miR-26 b-5 p和miR-146 a-5 p)在骨关节炎ACL组织中上调,而17种(包括miR-18 a-3 p、miR-138- 5 p和miR-485- 3 p)下调(倍数变化≥2,P值<0.05)。12个miRNAs的表达水平通过定量PCR进行验证,相应的结果显示了良好的相关性与芯片数据(R2=0.889)。参与软骨发育和重塑、胶原生物合成和降解、炎症反应和细胞外基质稳态的基因(如具有血小板反应蛋白1型基序的去整合素和金属蛋白酶结构域、骨形态发生蛋白2、侏儒相关转录因子2、胶原1A 1和2、白细胞介素6和转化生长因子β)被预测为失调的miRNA的潜在靶点。此外,OA发病相关的信号通路(如丝裂原活化蛋白激酶和血管内皮生长因子信号通路)中富含大量的推定基因。总的来说,我们的研究数据为OA患者韧带损伤相关的miRNA失调提供了新的见解。
The degradation of cruciate ligaments is frequently observed in degenerative joint diseases, such as osteoarthritis (OA). The present study aimed to identify the differentially expressed microRNAs (miRNAs or miRs) in knee anterior cruciate ligament (ACL) tissues derived from patients with OA and in health subjects (non-OA). By using Affymetrix miRNA 4.0 microarrays, a total of 22 miRNAs (including let-7f-5p, miR-26b-5p and miR-146a-5p) were found to be upregulated, while 17 (including miR-18a-3p, miR-138-5p and miR-485-3p) were downregulated in the osteoarthritic ACL tissues (fold change ≥2, P-value <0.05). The expression levels of 12 miRNAs were validated by quantitative PCR, and the corresponding results revealed an excellent correlation with the microarray data (R2=0.889). Genes (such as a disintegrin and metalloproteinase domain with thrombospondin type-1 motifs, bone morphogenetic protein-2, runt related transcription factor-2, collagen-1A1 and 2, interleukin-6 and transforming growth factor-β) involved in cartilage development and remodeling, collagen biosynthesis and degradation, inflammatory response and extracellular matrix homeostasis were predicted as potential targets of the dysregulated miRNAs. Moreover, a large set of putative genes were enriched in OA pathogenesis-associated pathways (such as mitogen-activated protein kinase and vascular endothelial growth factor signaling pathway). Collectively, the data from our study provides novel insight into the ligament injury-related miRNA dysregulation in patients with OA.
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