دورية أكاديمية
M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis
| العنوان: | M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis |
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| المؤلفون: | Chunyang Fan, Wei Wang, Zilin Yu, Jiale Wang, Wei Xu, Zhongwei Ji, Wei He, Di Hua, Wentao Wang, Linye Yao, Yongkang Deng, Dechun Geng, Xiexing Wu, Haiqing Mao |
| المصدر: | Journal of Nanobiotechnology, Vol 22, Iss 1, Pp 1-20 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Biotechnology LCC:Medical technology |
| مصطلحات موضوعية: | Macrophage, Exosome, LCN2, Intervertebral disc degeneration, Cellular senescence, Biotechnology, TP248.13-248.65, Medical technology, R855-855.5 |
| الوصف: | Abstract Intervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead to local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown the significance of M1-type macrophages in IVDD; nevertheless, the precise mechanism and the route by which it influences the function of nucleus pulposus cell (NPC) remain unknown. Utilizing a rat acupuncture IVDD model and an NPC degeneration model induced by lipopolysaccharide (LPS), we investigated the function of M1 macrophage-derived exosomes (M1-Exos) in IVDD both in vivo and in vitro in this study. We found that M1-Exos enhanced LPS-induced NPC senescence, increased the number of SA-β-gal-positive cells, blocked the cell cycle, and promoted the activation of P21 and P53. M1-Exos derived from supernatant pretreated with the exosome inhibitor GW4869 reversed this result in vivo and in vitro. RNA-seq showed that Lipocalin2 (LCN2) was enriched in M1-Exos and targeted the NF-κB pathway. The quantity of SA-β-gal-positive cells was significantly reduced with the inhibition of LCN2, and the expression of P21 and P53 in NPCs was decreased. The same results were obtained in the acupuncture-induced IVDD model. In addition, inhibition of LCN2 promotes the expression of type II collagen (Col-2) and inhibits the expression of matrix metalloproteinase 13 (MMP13), thereby restoring the equilibrium of metabolism inside the extracellular matrix (ECM) in vitro and in vivo. In addition, the NF-κB pathway is crucial for regulating M1-Exo-mediated NPC senescence. After the addition of M1-Exos to LPS-treated NPCs, p-p65 activity was significantly activated, while si-LCN2 treatment significantly inhibited p-p65 activity. Therefore, this paper demonstrates that M1 macrophage-derived exosomes have the ability to deliver LCN2, which activates the NF-κB signaling pathway, and exacerbates IVDD by accelerating NPC senescence. This may shed new light on the mechanism of IVDD and bring a fresh approach to IVDD therapy. Graphical Abstract |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1477-3155 |
| Relation: | https://doaj.org/toc/1477-3155 |
| DOI: | 10.1186/s12951-024-02556-8 |
| URL الوصول: | https://doaj.org/article/3fa3c22bfe5844cfb73a1968b14d6348 |
| رقم الأكسشن: | edsdoj.3fa3c22bfe5844cfb73a1968b14d6348 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 14773155 |
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| DOI: | 10.1186/s12951-024-02556-8 |