Exosomal miR-532-5p from bone marrow mesenchymal stem cells reduce intervertebral disc degeneration by targeting RASSF5

The transplantation of bone marrow mesenchymal stem cells (BMSCs) has been found to be used as an effective therapy of intervertebral disc degeneration (IDD). However, the underlying mechanisms of BMSCs in the progress of IDD are not fully explained. In this study, we found that exosomes derived from BMSCs (BMSCs-Exos) inhibited the apoptotic rate, extracellular matrix (ECM) degradation, and fibrosis deposition in TNF-alpha-induced nucleus pulposus cells (NPCs). Importantly, the level of miR-532-5p was observed to be decreased in apoptotic NPCs, but abundant in BMSCs-Exos with TNF-alpha treatment. The results showed that BMSCs-Exos under TNF-alpha stimuli exerted better effects on NPCs than BMSCs-Exos, which might be mitigated by the inhibition of miR-532-5p in BMSCs-Exos. The gain-of-function results suggested that the direct overexpression of miR-532-5p in NPCs could inhibit TNF-alpha-induced increase of apoptotic process, activation of apoptotic proteins, imbalance of anabolism/catabolism levels, and accumulation of collagen I. In addition, RASSF5 was demonstrated to be a target of miR-532-5p. Knockdown of RASSF5 could decrease the apoptotic cells and reduce the activated apoptotic protein levels in TNF-alpha-induced NPCs. Overall, these data indicate that exosomes from BMSCs may suppress TNF-alpha-induced apoptosis, ECM degradation, and fibrosis deposition in NPCs through the delivery of miR-532-5p via targeting RASSF5. This work provides a promising therapeutic strategy for the progress of IDD.