MicroRNA-338-3p as a novel therapeutic target for intervertebral disc degeneration

Recent studies have demonstrated the pivotal role played by microRNAs (miRNAs) in the etiopathogenesis of intervertebral disc degeneration (IDD). The study of miRNA intervention in IDD models may promote the advancement of miRNA-based therapeutic strategies. The aim of the current study was to investigate whether intradiscal delivery of miRNA can attenuate IDD development. Our results showed that 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 expression level 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 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 the MAPK/ERK pathway. Intradiscal injection of antagomir-338-3p significantly decelerated IDD development in mouse models. Our study is the first to identify miR-338-3p as a mediator of IDD and thus may be a promising target for rescuing IDD. Spine disease: how to halt disc degradation Development of intervertebral disc degeneration (IDD) is driven by a microRNA, a short noncoding segment of genetic material, called miR-338-3p, and blocking it may offer a path to better treatments. In IDD, a common spine disorder, the cushioning discs between vertebrae degenerate, leading to pain and loss of mobility. Current treatments address symptoms, not the root causes. Micro-RNAs have emerged as key contributors to skeletal disorders, and Qingjun Wei and Hua Jiang at Guangxi Medical University, Nanning, China, investigated their role in IDD. Screening of microRNAs in IDD patients showed that miR-338-3p levels were significantly elevated and correlated with IDD severity. Inhibiting miR-338-3p in cultured disc cells boosted their proliferation, and administering the inhibitor to a mouse model suppressed IDD development. These results may help in identifying new treatments for this common and debilitating condition.