Notochordal-Cell-Derived Exosomes Induced by Compressive Load Inhibit Angiogenesis via the miR-140-5p/Wnt/β-Catenin Axis

Molecular Therapy: Nucleic Acids

Bing Liu¹  Bei-Yu Chen²  Jing Fan³  Wen Song⁴  Dan Geng⁵  Zhuo-Jing Luo⁵  Zhe Xu⁵  Zhen Sun⁵  Zhi-Heng Liu⁶  Dong Wang⁷ 

[1] Corresponding author: Zhen Sun, Department of Orthopedic, Xijing Hospital, Fourth Military Medical University, Western Changle Road, Xi’an 710032, China.;;National Clinical Research Center for Oral Diseases &Shaanxi Key Laboratory of Oral Diseases, Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University, Xi’an 710032, China;Department of Orthopedic, 986 Air Force Hospital of China, Xi’an 710032, China;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;;State Key Laboratory of Military Stomatology &

关键词: intervertebral disc;    notochordal cell;    exosome;    angiogenesis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown