Melatonin activates autophagy via the NF-κB signaling pathway to prevent extracellular matrix degeneration in intervertebral disc

自噬 褪黑素 细胞外基质 体内 细胞生物学 免疫印迹 椎间盘 污渍 免疫组织化学 生物 化学 病理 内分泌学 解剖 医学 生物化学 免疫学 细胞凋亡 生物技术 基因
作者
Fan Chen,Haoran Liu,X. Wang,Zhenwei Li,Jiming Zhang,Yuxin Pei,Zhaomin Zheng,Jianru Wang
出处
期刊:Osteoarthritis and Cartilage [Elsevier]
卷期号:28 (8): 1121-1132 被引量:49
标识
DOI:10.1016/j.joca.2020.05.011
摘要

Summary

Objective

This study investigated whether melatonin alleviates intervertebral disc degeneration (IVDD) by promoting autophagy through inhibiting the NF-κB signaling pathway.

Methods

Magnetic resonance imaging (MRI), hematoxylin and eosin (H&E) staining and Safranin-O staining were used to measure disc degeneration in rat needle puncture IVDD models, and melatonin was injected intraperitoneally in the treated group to test its function. The expression of autophagy and extracellular matrix (ECM) degeneration related-markers were measured in the discs using immunohistochemistry. Transmission electron microscopy was used to evaluate the activation of autophagy in human nucleus pulposus (NP) tissues with different degenerated statuses. The expression of autophagy and disc degeneration related-markers were detected in NP cells by Western blot, RT-qPCR, and immunofluorescence analyses. NF-κB signaling pathway involvement was studied by lentivirus-mediated knockdown, Western blotting, and immunohistochemistry and immunofluorescence staining.

Results

Melatonin prevented IVDD development in vivo and in vitro. Compared to non-degenerated disc tissues, degenerated human NP tissues showed a decrease in the autophagy-specific marker LC3B and the numbers of autophagosomes and autolysosomes, whereas the p62 level was increased; similar results were observed in rat IVDD models, indicating a negative correlation between autophagy and IVDD. Furthermore, both in vivo and in vitro studies found that melatonin application induced autophagy and reduced ECM disc degradation. Melatonin was also shown to regulate autophagy by inhibiting the NF-κB signaling pathway in vivo and vitro.

Conclusion

This study indicates that melatonin prevents IVDD by promoting autophagy, indicating its possible therapeutic potential for controlling the progression of IVDD.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
XuanZhang发布了新的文献求助10
刚刚
1秒前
2秒前
2秒前
英姑应助大力出奇迹采纳,获得10
2秒前
Greetdawn完成签到,获得积分10
3秒前
3秒前
3秒前
5秒前
stories完成签到,获得积分10
5秒前
Hanaooooo发布了新的文献求助10
6秒前
呱呱完成签到,获得积分10
6秒前
ML发布了新的文献求助10
7秒前
cc发布了新的文献求助10
7秒前
8秒前
nsk810431231发布了新的文献求助10
8秒前
乐乐应助俏皮的未来采纳,获得10
8秒前
李小新发布了新的文献求助10
9秒前
不配.应助仓颉采纳,获得10
9秒前
舒心怀绿发布了新的文献求助10
9秒前
eee丶peng发布了新的文献求助10
9秒前
9秒前
10秒前
11秒前
11秒前
99giddens应助Kk采纳,获得10
11秒前
13秒前
jwb711发布了新的文献求助10
14秒前
14秒前
大力出奇迹完成签到,获得积分10
15秒前
FashionBoy应助忧伤的宝马采纳,获得10
15秒前
orixero应助科研通管家采纳,获得10
15秒前
彭于晏应助科研通管家采纳,获得10
15秒前
乐乐应助科研通管家采纳,获得10
15秒前
FashionBoy应助科研通管家采纳,获得10
15秒前
15秒前
彭于晏应助科研通管家采纳,获得10
15秒前
李爱国应助科研通管家采纳,获得10
15秒前
15秒前
15秒前
高分求助中
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
Rechtsphilosophie 1000
Bayesian Models of Cognition:Reverse Engineering the Mind 888
Very-high-order BVD Schemes Using β-variable THINC Method 568
Chen Hansheng: China’s Last Romantic Revolutionary 500
XAFS for Everyone 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3137977
求助须知:如何正确求助?哪些是违规求助? 2788907
关于积分的说明 7789001
捐赠科研通 2445272
什么是DOI,文献DOI怎么找? 1300255
科研通“疑难数据库(出版商)”最低求助积分说明 625878
版权声明 601046