MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2
MiR-34a promotes Fas-mediated cartilage endplate chondrocyte apoptosis by targeting Bcl-2
复制标题
MiR-34a通过靶向Bcl-2促进Fas介导的软骨终板软骨细胞凋亡
DOI：
10.1007/s11010-015-2420-4
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发表时间：
2015-08-01
影响因子：
4.3
通讯作者：
Yuan, Wen
中科院分区：
文献类型：
--
作者：
Chen, Huajiang;Wang, Jianxi;Yuan, Wen
软骨终板（CEP）软骨细胞凋亡与椎间盘退变（IDD）的发生有关。最近的研究表明，miR-34 a在骨关节炎软骨中至关重要地参与软骨细胞凋亡。在此，我们研究了miR-34 a在IDD CEP软骨细胞凋亡中的作用。在人退变的CEP软骨细胞中，miRNA（miR）-34a显著升高，与凋亡增加相关。生物信息学靶标预测将Bcl-2鉴定为miR-34 a的推定靶标。此外，miR-34 a通过直接靶向Bcl-2的3 '-非翻译区来抑制Bcl-2的表达，并且这种抑制通过miR-34 a结合位点的突变来消除。在体外，人终板软骨细胞中miR-34 a的敲低导致Bcl-2的过表达，而miR-34 a的上调导致Bcl-2的抑制。在人终板软骨细胞中，当用锁核苷酸类似物miR-34 a拮抗miR-34 a时，Fas介导的凋亡减少。综上所述，我们的结果表明，上调的miR-34 a增强Fas介导的终板软骨细胞凋亡，这与IDD相关。
Apoptosis of cartilage endplate (CEP) chondrocytes is associated with the pathogenesis of intervertebral disk degeneration (IDD). Recent studies have shown that miR-34a is crucially involved in chondrocyte apoptosis during osteoarthritic cartilage. Here, we investigated the involvement of miR-34a in CEP chondrocyte apoptosis in IDD. In human degenerated CEP chondrocytes, miRNA (miR)-34a was markedly elevated in association with increased apoptosis. Bioinformatics target prediction identified Bcl-2 as a putative target of miR-34a. Furthermore, miR-34a inhibited Bcl-2 expression by directly targeting their 3'-untranslated regions, and this inhibition was abolished by mutation of the miR-34a binding sites. In vitro, knockdown of miR-34a in human endplate chondrocytes resulted in overexpression of Bcl-2, whereas upregulation of miR-34a led to repression of Bcl-2. Fas-mediated apoptosis was decreased when antagonizing miR-34a with locked nucleotide analog-miR-34a in human endplate chondrocytes. Taken together, our results demonstrate that upregulated miR-34a potentiates Fas-mediated endplate chondrocyte apoptosis, which is associated with IDD.