MicroRNA-338-3p as A Novel Therapeutic Target for Intervertebral Disc Degeneration

Abstract Background: Recent studies have demonstrated the pivotal role played by microRNA (miRNA) in the etiopathogenesis of intervertebral disc degeneration (IDD). The aim of this current study is to investigate whether intra-discal delivery of miRNA can attenuate IDD development.Results: miR-338-3p expression was significantly increased in the nucleus pulposus (NP) of patients with IDD. Moreover, there was a statistically significant positive correlation between the level of expression of miR-338-3p and the severity of IDD. Our functional studies showed that miR-338-3p significantly influenced the expression of extracellular matrix synthesis of genes, as well as the proliferation and apoptosis of NP cells. Mechanistically, miR-338-3p aggravated IDD progression by directly targeting SIRT6, a negative regulator of MAPK/ERK pathway. Intra-discal injection of antagomir-338-3p significantly decelerated IDD development in mice models.Conclusions: miR-338-3p is identified as a mediator of IDD, and thus may be a promising target for rescuing IDD.