CircSEMA4B targets miR-431 modulating IL-1β-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway
CircSEMA4B targets miR-431 modulating IL-1β-induced degradative changes in nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway
复制标题
CircSEMA4B 靶向 miR-431 通过 Wnt 通路调节椎间盘退变中 IL-1 β 诱导的髓核细胞降解变化
DOI：
10.1016/j.bbadis.2018.08.033
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发表时间：
2018-11-01
影响因子：
6.2
通讯作者：
Lu, Chang
中科院分区：
文献类型：
--
作者：
Wang, Xiaobin;Wang, Bing;Lu, Chang
椎间盘（IVD）变性（IDD）的特征在于促炎介质水平升高、聚集蛋白聚糖和胶原降解增加以及细胞外基质（ECM）降解增加，已被广泛认为是腰痛的重要原因。遗传因素是IDD发病的重要因素。基于先前的数据，环状RNA SEMA 4 B（circSEMA 4 B）在IDD标本中下调;在此，我们证明了circSEMA 4 B过表达可以减弱IL-1 β对髓核细胞（NPC）增殖、衰老以及ECM和聚集蛋白聚糖降解的影响。此外，miR-431作为circSEMA 4 B的直接靶点，可以结合Wnt信号的两种抑制性调节剂SERPI或GSK-3 β的3 'UTR，以抑制它们的表达，从而在NPC中发挥类似于Wnt信号激活剂的作用。circSEMA 4 B敲低对NPC的影响被miR-431抑制部分逆转; circSEMA 4 B作为miR-431海绵与SERPI或GSK-313竞争miR-431结合，从而通过Wnt信号传导抑制NPC中IL-1 β诱导的退行性过程。在IDD的NPC中拯救circSEMA 4 B表达可能是IDD改善的潜在策略。
Intervertebral disc (IVD) degeneration (IDD), characterized by elevated levels of proinflammatory mediators, increased Aggrecan and collagen degradation, and increased degradation of extracellular matrix (ECM), has been widely regarded as a significant contributor to low back pain. Genetics are significant factors contribute to IDD. Based on previous data, circular RNA SEMA4B (circSEMA4B) is down-regulated in IDD specimens; herein, we demonstrated circSEMA4B overexpression could attenuate the effect of IL-1 beta on nucleus pulposus cell (NPC) proliferation, senescence, and ECM and Aggrecan degradation in IDD via Wnt signaling. Moreover, miR-431, a direct target of circSEMA4B, could bind to the 3'UTR of SERPI or GSK-3 beta, two inhibitory regulators of Wnt signaling, to inhibit their expression thus playing a role similar to the activator of Wnt signaling in NPCs. The effect of circSEMA4B knockdown on NPCs was partially reversed by miR-431 inhibition; circSEMA4B serves as a miR-431 sponge to compete with SERPI or GSK-313 for miR-431 binding, thus inhibiting IL-1 beta-induced degenerative process in NPCs through Wnt signaling. Rescuing circSEMA4B expression in NPCs in IDD might present a potential strategy for IDD improvement.