Sun Zhen, Liu Bing, Liu Zhi-Heng, Song Wen, Wang Dong, Chen Bei-Yu, Fan Jing, Xu Zhe, Geng Dan, Luo Zhuo-Jing
Department of Orthopedic, Xijing Hospital, Fourth Military Medical University, Western Changle Road, Xi'an 710032, China.
Department of Radiology, Xijing Hospital, Fourth Military Medical University, Western Changle Road, Xi'an 710032, China.
Mol Ther Nucleic Acids. 2020 Oct 22;22:1092-1106. doi: 10.1016/j.omtn.2020.10.021. eCollection 2020 Dec 4.
Angiogenesis is a pathological signature of intervertebral disc degeneration (IDD). Accumulating evidence has shown that notochordal cells (NCs) play an essential role in maintaining intervertebral disc development and homeostasis with inhibitive effect on blood vessel in-growth. However, the anti-angiogenesis mechanism of NCs is still unclear. In the current study, we, for the first time, isolated NC-derived exosomes (NC-exos) and showed their increased concentration following compressive load cultures. We further found that NC-exos from 0.5 MPa compressive load cultures (0.5 MPa/NC-exos) inhibit angiogenesis via transferring high expressed microRNA (miR)-140-5p to endothelial cells and regulating the downstream Wnt/β-catenin pathway. Clinical evidence showed that exosomal miR-140-5p expression of the nucleus pulposus is negatively correlated with angiogenesis in IDD. Finally, 0.5 MPa/NC-exos were demonstrated to have a therapeutical impact on the degenerated disc with an anti-angiogenesis effect in an IDD model. Consequently, our present findings provide insights into the anti-angiogenesis mechanism of NC-exos, indicating their therapeutic potential for IDD.
血管生成是椎间盘退变（IDD）的一个病理特征。越来越多的证据表明，脊索细胞（NCs）在维持椎间盘发育和内环境稳定中起着至关重要的作用，对血管向内生长具有抑制作用。然而，NCs的抗血管生成机制仍不清楚。在本研究中，我们首次分离出NC来源的外泌体（NC-exos），并发现其在压缩负荷培养后浓度增加。我们进一步发现，来自0.5MPa压缩负荷培养的NC-exos（0.5MPa/NC-exos）通过将高表达的微小RNA（miR）-140-5p转移至内皮细胞并调节下游Wnt/β-连环蛋白通路来抑制血管生成。临床证据表明，髓核中外泌体miR-140-5p的表达与IDD中的血管生成呈负相关。最后，在IDD模型中，0.5MPa/NC-exos被证明对退变椎间盘具有治疗作用，并具有抗血管生成效应。因此，我们目前的研究结果为NC-exos的抗血管生成机制提供了见解，表明它们对IDD具有治疗潜力。
