MiR-26a and miR-26b mediate osteoarthritis progression by targeting FUT4 via NF-κB signaling pathway
MiR-26a and miR-26b mediate osteoarthritis progression by targeting FUT4 via NF-κB signaling pathway
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DOI：
10.1016/j.biocel.2017.12.003
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Jia, Li
中科院分区：
文献类型：
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作者：
Hu, Jialei;Wang, Zi;Jia, Li
骨关节炎（OA）是最常见的关节疾病，其特征是关节软骨退化和所有其他关节组织的变化。MicroRNAs （miRNAs）在介导OA的主要危险因素中发挥重要作用。本研究旨在通过NF-kappa B信号通路靶向聚焦转移酶4 (FUT4)，探讨miR-26a/26b对人软骨细胞增殖和凋亡的影响。我们揭示了FUT4和miR-26a/26b在OA患者和正常人关节软骨组织中的差异表达谱。miR-26a/26b与FUT4的3'UTR特异性相互作用的能力是通过软骨细胞中的荧光素酶报告基因试验证明的。进一步的结果表明，miR-26a/26b和FUT4水平的改变可以调节IL-1 β诱导的软骨细胞细胞外基质降解过程。miR-26a/26b的强制表达能够影响软骨细胞的增殖和凋亡，而转染miR-26a/26b模拟物或抑制剂后，软骨细胞中FUT4表达的改变调节了软骨细胞的进展。在OA小鼠中，通过关节内注射过表达miR-26a/26b可显著减弱OA进展。此外，调节FUT4的表达可显著调节NF-kappa B信号通路的活性，这种作用可被miR-26a/26b逆转。总之，miR-26a/-26b/FUT4/NF-kappa B轴可能作为OA治疗的预测性生物标志物和潜在的治疗靶点。
Osteoarthritis (OA) is the most common joint disease, characterized by articular cartilage degradation and changes in all other joint tissues. MicroRNAs (miRNAs) play an important role in mediating the main risk factors for OA. This study aimed to investigate the effect of miR-26a/26b on the proliferation and apoptosis of human chondrocytes by targeting fucosyltransferase 4 (FUT4) through NF-kappa B signaling pathway. We revealed the differential expression profiles of FUT4 and miR-26a/26b in the articular cartilage tissues of OA patients and normal people. The ability of miR-26a/26b to specifically interact with the 3'UTR of FUT4 was demonstrated via a luciferase reporter assay in chondrocytes. Further results showed altered levels of miR-26a/26b and FUT4 could regulate the process of IL-1 beta-induced extracellular matrix degradation in chondrocytes. Forced miR-26a/26b expression was able to affect chondrocytes proliferation and apoptosis, while altered expression of FUT4 in chondrocytes modulated progression upon transfection with miR-26a/26b mimic or inhibitor. In OA mice, the overexpression of miR-26a/26b by intra-articular injection significantly attenuated OA progression. In addition, regulating FUT4 expression markedly modulated the activity of NF-kappa B signaling pathway, and this effect could be reversed by miR-26a/26b. In short, miR-26a/-26b/FUT4/NF-kappa B axis may serve as a predictive biomarker and a potential therapeutic target in OA treatment.