MicroRNA-146a-5p inhibits recruitment of macrophages and protects nucleus pulposus cells from TNF-α-induced apoptosis by targeting TRAF6

Intervertebral disc degeneration (IDD) is associated with lower back pain and plays an important role in the development of spinal disc herniation. In this study, we aimed to analyze expression and function of inflammation-associated microRNA-146a-5p (miR-146a-5p) in IDD. We found that miR-146a-5p expression was significantly reduced in bulging and herniated lumbar disc, and the levels of tumour necrosis factor a (TNF-alpha) and human tumour necrosis factor receptor type 1 (TNFR1) had a positive relationship with lumbar disc herniation severity types. In vitro, miR-146a-5p up-regulation inhibited TNF-alpha-induced human nucleus pulposus (NP) cells apoptosis and recruitment of macrophages. Conversely, the down-regulation of miR-146a-5p reversed these effects. Tumor necrosis factor receptor-associated factor 6 (TRAF6), a potential target gene of miR-146a-5p, was inversely correlated with miR-146a-5p expression in clinical NP. Furthermore, we also revealed that TRAF6 is a target of miR-146a-5p and re-expression of TRAF6 reversed the inhibitory effects of miR-146a-5p on NP cells apoptosis and macrophages recruitment. Taking together, miR-146a-5p may play a critical role in intervertebral disc degeneration and herniation by targeting the TRAF6 expression in NP cells.