MiR-140-5p转录后调控SIAH1诱发椎间盘软骨终板退变的作用机制

The diseases of degeneration of intervertebral disc consisted of cervical spondylosis and lumbar disc herniation. The incidence of degeneration of intervertebral disc was significantly increasing in recent years. The degeneration of cartilage end-plate could be considered as the cause of degeneration of intervertebral disc. So far, the mechanism of degeneration of cartilage end-plate is still uncertain. The authors first of all observed that miR-140-5p was low-expression, and found that target gene of miR-140-5p, SIAH1, demonstrated over-expression in the human cartilage end-plate of degeneration. SIAH1 could activate HIF-1and JNK/Bim signal pathway, resulting in the overexpression of VEGF and cell apoptosis. The overexpression of VEGF and cell apoptosis was closely associated with degeneration of cartilage end-plate. Thus, the authors proposed the hypothesis that miR-140-5p participated in regulating the degeneration of cartilage end-plate through SIAH1 activating HIF-1and JNK/Bim signal pathway. We were intended to employ the technology of luciferase further validating the target control role between miR-140-5p and SIAH1. Meanwhile, we analyzed the role and expression of downstream signal pathway of SIAH1 on cartilage end-plate. The strategy of gene silencing in the rhesus was also performed in order to reveal the role of miR-140-5p on the degeneration of cartilage end-plate. Analysing the role of miR-140-5p on the degeneration of cartilage end-plate would be a novel viewpoint revealing the potential pathogenesis and curing the degeneration of intervertebral disc.

椎间盘退变性疾病包括颈椎病和腰椎间盘突出症，发病率逐年增加。软骨终板退变是椎间盘退变的始动因素。目前，软骨终板退变的分子机制尚不明确。课题组发现miR-140-5p在人退变的软骨终板中低表达，候选靶基因SIAH1呈对应性高表达。SIAH1可激活HIF-1和JNK/Bim信号通路,诱发VEGF高表达和细胞凋亡。VEGF高表达和凋亡与终板软骨细胞退变发生、发展密切相关。推测：miR-140-5p调控SIAH1，激活HIF-1和JNK/Bim信号通路诱发软骨终板退变。我们拟通过荧光素酶等方法，进一步验证miR-140-5p与SIAH1靶向关系；分析SIAH1下游信号通路在终板软骨细胞中的表达和作用；体内、外基因沉默实验揭示miR-140-5p在软骨终板退变中的作用。本研究从miR-140-5p这个新视点为揭示软骨终板退变的发病机制奠定基础，为日后通过靶点治疗椎间盘退变提供新思路。

椎间盘退变性疾病包括颈椎病和腰椎间盘突出症，发病率逐年增加。软骨终板退变是椎间盘退变的始动因素。目前，软骨终板退变的分子机制尚不明确。课题组发现miR-140-5p在人退变的软骨终板中低表达，候选靶基因SIAH1呈对应性高表达。SIAH1可激活HIF-1和JNK/Bim信号通路,诱发VEGF高表达和细胞凋亡。VEGF高表达和凋亡与终板软骨细胞退变发生、发展密切相关。推测：miR-140-5p调控SIAH1，激活HIF-1和JNK/Bim信号通路诱发软骨终板退变。我们拟通过荧光素酶等方法，进一步验证miR-140-5p与SIAH1靶向关系；分析SIAH1下游信号通路在终板软骨细胞中的表达和作用；体内、外基因沉默实验揭示miR-140-5p在软骨终板退变中的作用。本研究从miR-140-5p这个新视点为揭示软骨终板退变的发病机制奠定基础，为日后通过靶点治疗椎间盘退变提供新思路。