Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats
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 mec...
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Wiley
2019-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2019/8404168 |
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| author | Wei-ren Lan Sai Pan Hai-yin Li Chao Sun Xian Chang Kang Lu Chang-qing Jiang Rui Zuo Yue Zhou Chang-qing Li |
| author_facet | Wei-ren Lan Sai Pan Hai-yin Li Chao Sun Xian Chang Kang Lu Chang-qing Jiang Rui Zuo Yue Zhou Chang-qing Li |
| author_sort | Wei-ren Lan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0ef9cddb4108450e952bab9acb1be790 |
| institution | OA Journals |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-0ef9cddb4108450e952bab9acb1be7902025-08-20T02:02:26ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/84041688404168Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in RatsWei-ren Lan0Sai Pan1Hai-yin Li2Chao Sun3Xian Chang4Kang Lu5Chang-qing Jiang6Rui Zuo7Yue Zhou8Chang-qing Li9Department of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Nephrology, General Hospital of PLA, Beijing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaDepartment of Orthopedic, The Second Affiliated Hospital of Army Medical University (The Third Military Medical University), Chongqing, ChinaStem 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.http://dx.doi.org/10.1155/2019/8404168 |
| spellingShingle | Wei-ren Lan Sai Pan Hai-yin Li Chao Sun Xian Chang Kang Lu Chang-qing Jiang Rui Zuo Yue Zhou Chang-qing Li Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats Stem Cells International |
| title | Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats |
| title_full | Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats |
| title_fullStr | Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats |
| title_full_unstemmed | Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats |
| title_short | Inhibition of the Notch1 Pathway Promotes the Effects of Nucleus Pulposus Cell-Derived Exosomes on the Differentiation of Mesenchymal Stem Cells into Nucleus Pulposus-Like Cells in Rats |
| title_sort | inhibition of the notch1 pathway promotes the effects of nucleus pulposus cell derived exosomes on the differentiation of mesenchymal stem cells into nucleus pulposus like cells in rats |
| url | http://dx.doi.org/10.1155/2019/8404168 |
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