Nucleus Pulposus-Targeting Nanocarriers Facilitate Mirna-Based Therapeutics for Intervertebral Disc Degeneration.

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, we conducted miRNA microarray analyses in conjunction with in vivo and in vitro experiments. The miR-22-3p knockout (KO) mice showed a marked decrease in the histological scores. Bioinformatic analysis revealed 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 was confirmed by a luciferase reporter assay and western blot analysis. Therapeutically, the delivery of miR-22-3p inhibitors and mimics through our synthesized nanoparticles in the IDD model alleviated and aggravated IDD, respectively. The nanocarriers enhanced transportation of miR-22-3p to nucleus pulposus (NP) 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. This article is protected by copyright. All rights reserved.