TSG-6 secreted by bone marrow mesenchymal stem cells attenuates intervertebral disc degeneration by inhibiting the TLR2/NF-κB signaling pathway

Abstract

Inflammation has been correlated with intervertebral disc degeneration (IDD). Recent evidence suggests that TNF-α-stimulated gene 6 protein (TSG-6) secreted by bone marrow mesenchymal stem cells (BMSCs) displays a remarkable ability to inhibit inflammatory processes in a variety of diseases. However, it is unknown whether BMSCs exert their therapeutic effect against IDD by secreting TSG-6. Here we investigated the effects of BMSCs and TSG-6 on IDD and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs and TSG-6 reduced the expression of MMP-3 and MMP-13, and increased the expression of collagen II and aggrecan in the IL-1β-treated nucleus pulposus cells (NPCs), but the protective effects of BMSCs and TSG-6 were attenuated when TSG-6 expression was silenced. We also found that the activation of the TLR2/NF-κB pathway was inhibited by BMSCs and TSG-6. The levels of IL-6 and TNF-α in the degenerated NPCs were reduced and the proliferation of IL-1β-treated NPCs was increased in the presence of BMSCs and TSG-6. Furthermore, in vivo experiments showed that BMSCs and TSG-6 restored the MRI T2-weighted signal intensity and increased collagen II and aggrecan expression in the degenerated nucleus pulposus (NP) tissues. Finally, our results showed that BMSCs and TSG-6 downregulated the TLR2/NF-κB signaling and reduced the expression of MMPs and inflammatory cytokines in the degenerated NP tissues. The present study is the first to demonstrate the involvement of TLR2/NF-κB pathway in the potential anti-IDD therapeutic effect of TSG-6, and the results provide new insight into the beneficial effect of BMSCs in the treatment of IDD.