1 Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
2 Department of Orthopaedic, First Affiliated Hospital, School of Medicine, Shihezi University, ShiHeZi, Xinjiang, China.
Exp Biol Med (Maywood). 2018 Apr;243(7):595-600. doi: 10.1177/1535370218760774. Epub 2018 Mar 13.
Intervertebral disc degeneration is a complex disease involving genetic and environmental factors and multiple cellular processes. The role and expression of the lncRNA NEAT1 were assessed in intervertebral disc degeneration. NEAT1 expression was assessed in degenerative and control nucleus pulposus using RT-PCR. Western blotting and RT-PCR were also used to investigate p53 and p21 levels in nucleus pulposus tissues. NEAT1 function in degenerative nucleus pulposus cells was assessed with gain- and loss-of-function experiments. ERK/MAPK signaling was also examined. NEAT1, p53, and p21 were dramatically upregulated in intervertebral disc degeneration. Furthermore, catabolic MMP13 and ADAMTS5 were dysregulated and collagen II and aggrecan were downregulated after NEAT1 overexpression. This effect was reversed by transfection with si-NEAT1 in degenerative nucleus pulposus cells. In addition, NEAT1 was found to affect the activation of the ERK/MAPK pathway. The NEAT1-induced ECM degradation may involve ERK1/2/MAPK signaling. LncRNA NEAT1 may represent a novel molecular target for intervertebral disc degeneration treatment by preventing nucleus pulposus ECM degradation. Impact statement For the first time, our study demonstrates that lncRNA NEAT1 plays a role in the occurrence and development of IDD by participating in extracellular matrix remodeling. This lncRNA regulates catabolic MMP13 and ADAMTS5 and anabolic collagen II and aggrecan by affecting the ERK/MAPK signaling pathway in degenerative human nucleus pulposus (NP) cells. Our research provides a scientific basis for targeting of NEAT1 for the IDD.
椎间盘退变是一种涉及遗传和环境因素以及多种细胞过程的复杂疾病。本研究评估了长链非编码 RNA NEAT1 在椎间盘退变中的作用和表达。采用 RT-PCR 检测退变和对照髓核组织中 NEAT1 的表达。还采用 Western blot 和 RT-PCR 检测髓核组织中 p53 和 p21 的水平。采用 gain-和 loss-of-function 实验评估 NEAT1 在退变髓核细胞中的功能。还检查了 ERK/MAPK 信号通路。NEAT1、p53 和 p21 在椎间盘退变中显著上调。此外，在过表达 NEAT1 后，代谢性 MMP13 和 ADAMTS5 失调，胶原 II 和聚集蛋白聚糖下调。在退变髓核细胞中转染 si-NEAT1 可逆转这种效应。此外，发现 NEAT1 影响 ERK/MAPK 通路的激活。NEAT1 诱导的细胞外基质降解可能涉及 ERK1/2/MAPK 信号通路。长链非编码 RNA NEAT1 可能通过防止髓核细胞外基质降解成为椎间盘退变治疗的新分子靶点。研究意义 本研究首次证明，长链非编码 RNA NEAT1 通过参与细胞外基质重塑在 IDD 的发生和发展中发挥作用。该 lncRNA 通过影响退变人髓核（NP）细胞中的 ERK/MAPK 信号通路调节代谢性 MMP13 和 ADAMTS5 以及合成代谢性胶原 II 和聚集蛋白聚糖。我们的研究为针对 NEAT1 治疗 IDD 提供了科学依据。
