Nucleus Pulposus‐Targeting Nanocarriers Facilitate Mirna‐Based Therapeutics for Intervertebral Disc Degeneration
Zhonghui Chen, Zhong Liao, Ming Liu, Fengfei Lin, Shunyou Chen, Geng Wang, Zhong Zheng, Boling Liu, Chaoxiong Li, Zheqiang Wang, Tianlai Chen, Hongzhe Huang, Qi Liao, W. Cui
Abstract
Intervertebral disc degeneration (IDD) is a common cause of low back pain. Understanding its molecular mechanisms is the basis for developing specific treatment. To demonstrate that miR-22-3p is critical in the regulation of IDD, miRNA microarray analyses are conducted in conjunction with in vivo and in vitro experiments. The miR-22-3p knockout (KO) mice show a marked decrease in the histological scores. Bioinformatic analysis reveals that miR-22-3p plays a mechanistic role in the development of IDD by targeting SIRT1, which in turn activates the JAK1/STAT3 signaling pathway. This is confirmed by a luciferase reporter assay and western blot analysis. Therapeutically, the delivery of miR-22-3p inhibitors and mimics through the synthesized nanoparticles in the IDD model alleviates and aggravates IDD, respectively. The nanocarriers enhance transportation of miR-22-3p to nucleus pulposus cells, thus enabling the in vivo inhibition of miR-22-3p for therapeutic purposes and consequently promoting the development of miRNA-specific drugs for IDD.