Cationic Polymer Brush-Modified Carbon Nanotube-Meditated eRNA LINC02569 Silencing Attenuates Nucleus Pulposus Degeneration by Blocking NF-κB Signaling Pathway and Alleviate Cell Senescence

Frontiers in Cell and Developmental Biology

Xiaoshuai Wang¹  Yulin Huang²  Ningning Chen²  Shaoyu Liu²  Baozhu Zeng²  Jiaming Yang²  Fuxin Wei²  Xizhe Liu³  Zemin Ling⁴  Kai Zhu⁵ 

[1] Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China;Department of Orthopedics Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China;Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology/Orthopaedic Research Institute, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China;Orthopaedic Section II, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, China;

关键词: Enhancer RNA;    intervertebral disc degeneration;    carbon nanotube;    inflammation;    senescence;   

DOI  :  10.3389/fcell.2021.837777

来源: DOAJ

【 摘 要 】

Enhancer RNAs (eRNAs) are noncoding RNAs that synthesized at active enhancers. eRNAs have important regulatory characteristics and appear to be significant for maintenance of cell identity and information processing. Series of functional eRNAs have been identified as potential therapeutic targets for multiple diseases. Nevertheless, the role of eRNAs on intervertebral disc degeneration (IDD) is still unknown yet. Herein, we utilized the nucleus pulposus samples of patients and identified a key eRNA (LINC02569) with the Arraystar eRNA Microarray. LINC02569 mostly locates in nucleus and plays an important role in the progress of IDD by activating nuclear factor kappa-B (NF-κB) signaling pathway. We used a cationic polymer brush coated carbon nanotube (oCNT-pb)-based siRNA delivery platform that we previously designed, to transport LINC02569 siRNA (si-02569) to nucleus pulposus cells. The siRNA loaded oCNT-pb accumulated in nucleus pulposus cells with lower toxicity and higher transfection efficiency, compared with the traditional siRNA delivery system. Moreover, the results showed that the delivery of si-02569 significantly alleviated the inflammatory response in the nucleus pulposus cells via inhibiting P65 phosphorylation and preventing its transfer into the nucleus, and meanwhile alleviated cell senescence by decreasing the expression of P21. Altogether, our results highlight that eRNA (LINC02569) plays important role in the progression of IDD and could be a potential therapeutic target for alleviation of IDD.

【 授权许可】

Unknown