Abstract
Stem cell therapies for intervertebral disc degeneration have been demonstrated as a promising strategy. Previous studies have shown that human nucleus pulposus cell- (NPC-) derived exosomes can induce the differentiation of mesenchymal stem cells (MSCs) into NP-like cells in vitro. However, the mechanism of MSC differentiation into NP-like cells with the induction of NPC exosomes is still unclear. Here, we verified the induction effects of NPC exosomes on the differentiation of MSCs into NP-like cells. In addition, the Notch1 pathway was downregulated in this process. Then, DAPT and soluble Jagged1 (SJAG) were applied to inhibit or enhance the expression of the Notch1 pathway, respectively, resulting in the upregulation or downregulation of collagen II, aggrecan, and Sox9 in MSCs. Knocking down of Notch1 protein facilitated the effects of NPC exosomes on the differentiation of MSCs into NP-like cells. NPC exosomes were more effective than an indirect coculture system in terms of the differentiation of MSCs into NP-like cells. Inhibition of NPC exosome secretion with Rab27a siRNA prevented the induction effects of an indirect coculture system on the differentiation of MSCs into NP-like cells. Transwell migration assays revealed that NPC exosomes could promote the migration of MSCs. Taken together, the Notch1 pathway was negatively associated with the differentiation of MSCs into NP-like cells with the treatments of NPC exosomes. Inhibition of the Notch1 pathway facilitates NPC exosome-induced differentiation of MSCs into NP-like cells in vitro. NPC exosomes play a key role in the differentiation of MSCs into NP-like cells in an indirect coculture system of NPCs and MSCs.
Highlights
Intervertebral disc degeneration (IDD) is one of the causes of low back pain [1]
The expression of collagen II, aggrecan, and Sox9 in mesenchymal stem cells (MSCs) cocultured with Rab27a siRNA-treated NPCs decreased significantly (Figures 5(e) and 5(f)). These results suggested that exosomes played a key role in MSC differentiation in an indirect coculture system
This study confirmed the induction effect of NPC exosomes on the differentiation of MSCs into NP-like cells, and it is more effective than an indirect coculture system
Summary
Intervertebral disc degeneration (IDD) is one of the causes of low back pain [1]. Traditional treatments mainly focus on symptomatic relief. Our previous study has found that human NPC-derived exosomes can induce MSC differentiation into NP-like cells [14]. We speculate that the Notch pathway is involved in exosome-induced differentiation of MSCs into NPCs. In this study, we explored the differential expression of the Notch pathway in exosome-induced differentiation of MSCs into NP-like cells and further explored its role by enhancing or inhibiting the Notch pathway. We investigated whether the inhibition of Notch could promote the exosome-induced differentiation of MSCs. we compared the inducing efficiency of NPC exosomes with an indirect coculture system on the differentiation of MSCs into NP-like cells and explored the role of NPC exosomes in an indirect coculture system by the inhibition of exosome secretion
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
