scholarly journals Mechanical loading mediates human nucleus pulposus cell viability and extracellular matrix metabolism by activating of NF‑κB

Author(s):  
Kai Zhang ◽  
Chao Xue ◽  
Ning Lu ◽  
Peng Ren ◽  
Haiwen Peng ◽  
...  
2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Yiyang Wang ◽  
Yanzhu Hu ◽  
Haoming Wang ◽  
Ningyuan Liu ◽  
Lei Luo ◽  
...  

Established studies proved that mechanical compression loading had multiple effects on the biological behavior of the intervertebral disc (IVD). However, the regulating mechanism involved in this process remains unclear. The current study is aimed at exploring the potential bioregulators and signaling pathways involved in the compression-associated biological changes of nucleus pulposus (NP) cells. Tandem mass tag- (TMT-) based quantitative proteomics was exerted to analyze the differentially expressed proteins (DEPs) and signal pathways among the different groups of NP cells cultured under noncompression, low-compression (LC), and high-compression (HC) loading. Eight potential protective bioregulators for the NP cell survival under different compression loading were predicted by the proteomics, among which macrophage migration inhibitory factor (MIF) and oxidative stress-related pathways were selected for further evaluation, due to its similar function in regulating the fate of the cartilage endplate- (CEP-) derived cells. We found that deficiency of MIF accentuates the accumulation of ROS, mitochondrial dysfunction, and senescence of NP cells under overloaded mechanical compression. The potential molecular mechanism involved in this process is related to the mitophagy regulating role of MIF. Our findings provide a better understanding of the regulatory role of mechanical compression on the cellular fate commitment and matrix metabolism of NP, and the potential strategies for treating disc degenerative diseases via using MIF-regulating agents.


2021 ◽  
Vol 12 ◽  
Author(s):  
Liang Tan ◽  
Yifang Xie ◽  
Ye Yuan ◽  
Kai Hu

The role of lncRNA growth arrest specific 5 (GAS5) in degenerative nucleus pulposus cell (NPC) apoptosis has been reported, but the mechanism of GAS5 in extracellular matrix (ECM) synthesis in intervertebral disc degeneration (IDD) remains unknown. We aimed to investigate the mechanism of GAS5 in ECM synthesis in degenerative NPCs. GAS5 expression was measured in degenerative NPCs (CP-H170) and normal NPCs (CP-H097). siRNA-mediated GAS5 knockdown was transfected to NPCs to detect cell viability and the expression of ECM-related genes (Collagen II, aggrecan, Collagen I, and MMP-3). Subcellular localization of GAS5 was analyzed. The downstream gene and pathway of GAS5 in degenerative NPCs were explored. As our results indicated, lncRNA GAS5 was upregulated in degenerative NPCs. Silencing GAS5 improved the viability of degenerative NPCs and increased ECM synthesis. GAS5 was mainly located in the cytoplasm of NPCs. LncRNA GAS5 sponged miR-26a-5p to regulate PTEN. Overexpression of miR-26a-5p promoted ECM synthesis in degenerative NPCs. Akt inhibitor LY294002 reversed the promotion of silencing GAS5 on ECM synthesis of degenerative NPCs. In conclusion, lncRNA GAS5 sponged miR-26a-5p to upregulate PTEN and inhibit the PI3K/Akt pathway, thus inhibiting ECM synthesis of degenerative NPCs.


2016 ◽  
Vol 6 (1_suppl) ◽  
pp. s-0036-1582626-s-0036-1582626
Author(s):  
Wai-Kit Tam ◽  
Kenneth M. C. Cheung ◽  
Victor Y. L. Leung

Spine ◽  
2006 ◽  
Vol 31 (9) ◽  
pp. 959-966 ◽  
Author(s):  
Koji Akeda ◽  
Howard S. An ◽  
Rajeswari Pichika ◽  
Mohamed Attawia ◽  
Eugene J.-M. A. Thonar ◽  
...  

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