Notochordal Cells-derived Exosomes Induced by Compressive Load Inhibit Angiogenesis via miR-140-5p/Wnt/β-catenin Axis: Implications for Intervertebral Disc Degeneration Treatment

Abstract 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 ingrowth. However, the anti-angiogenesis mechanism of NCs is still unclear. In the current study, we for the first time isolated NCs-derived exosomes (NCs-exos) and showed their increased concentration following compressive load cultures. We further found that NCs-exos from 0.5MPa compressive load cultures (0.5MPa/NCs-exos) inhibit angiogenesis via transferring high expressed miR-140-5p to endothelial cells and regulating downstream Wnt//β-catenin pathway. Clinical evidence showed that exosomal miR-140-5p expression of nucleus pulposus is negatively correlated with angiogenesis in IDD. Finally, 0.5MPa/NCs-exos were demonstrated to have therapeutical impact on degenerated disc with anti-angiogenesis effect in an IDD model. Consequently, our present findings provide insights into the anti-angiogenesis mechanism of NCs-exos, indicating their therapeutic potential for IDD.