Cardamonin protects nucleus pulposus cells against IL-1β-induced inflammation and catabolism via Nrf2/NF-κB axis

2021 ◽  
Author(s):  
Chenglong Xie ◽  
Haiwei Ma ◽  
Yifeng Shi ◽  
Junli Li ◽  
Hongqiang Wu ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Nucleus Pulposus Cells ◽  
Ecm Degradation

IL-1β promotes inflammatory response and extracellular matrix (ECM) degradation through NF-κB signaling pathway; while cardamonin attenuates the inflammatory response and ECM degradation by suppressing NF-κB signaling pathway via Nrf2/HO-1 axis.

scholarly journals Periodic Mechanical Stress Induces Extracellular Matrix Expression and Migration of Rat Nucleus Pulposus Cells Through Src-GIT1-ERK1/2 Signaling Pathway

2018 ◽  
Vol 50 (4) ◽  
pp. 1510-1521 ◽  
Author(s):  
Gongming Gao ◽  
Haibo Li ◽  
Yongjing Huang ◽  
Jianjian Yin ◽  
Yuqing Jiang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Mechanical Stress ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Signal Transduction Pathway ◽  
Direct Interaction ◽  
Nucleus Pulposus Cells ◽  
Immunoprecipitation Assay ◽  
And Migration

Background/Aims: Periodic mechanical stress has been shown to promote extracellular matrix (ECM) synthesis and cell migration of nucleus pulposus (NP) cells, however, the mechanisms need to be fully elucidated. The present study aimed to investigate the signal transduction pathway in the regulation of NP cells under periodic mechanical stress. Methods: Primary rat NP cells were isolated and seeded on glass slides, and then treated in our self-developed periodic stress field culture system. To further explore the mechanisms, data were analyzed by scratch-healing assay, quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, western blotting, and co-immunoprecipitation assay. Results: Under periodic mechanical stress, the mRNA expression of ECM collagen 2A1 (Col2A1) and aggrecan, and migration of NP cells were significantly increased (P < 0.05 for each), associating with increases in the phosphorylation of Src, GIT1, and ERK1/2 (P < 0.05 for each). Pretreatment with the Src inhibitor PP2 reduced periodic mechanical stress-induced ECM synthesis and cell migration of NP cells (P < 0.05 for each), while the phosphorylation of GIT1 and ERK1/2 were inhibited. ECM synthesis, cell migration, and phosphorylation of ERK1/2 were inhibited after pretreatment with the small interfering RNA for GIT1 in NP cells under periodic mechanical stress (P < 0.05 for each), whereas the phosphorylation of Src was not affected. Pretreatment with the ERK1/2 inhibitor PD98059 reduced periodic mechanical stress-induced ECM synthesis and cell migration of NP cells (P < 0.05 for each). Co-immunoprecipitation assay showed that there was a direct interaction between Src and GIT1 and between GIT1 and ERK1/2. Conclusion: In conclusion, periodic mechanical stress induced ECM expression and migration of NP cells via Src-GIT1-ERK1/2 signaling pathway, playing an important role in regulation of NP cells.

BMP9 Promotes the Extracellular Matrix of Nucleus Pulposus Cells via Inhibition of the Notch Signaling Pathway

2019 ◽  
Vol 38 (4) ◽  
pp. 358-366
Author(s):  
Xiang Zhang ◽  
Bo Qiao ◽  
Zhenming Hu ◽  
Weidong Ni ◽  
Shuquan Guo ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Notch Signaling Pathway ◽  
Nucleus Pulposus Cells

scholarly journals Human Bone Marrow Mesenchymal Stromal Cell-Derived Extracellular Vesicles Promote Proliferation of Degenerated Nucleus Pulposus Cells and the Synthesis of Extracellular Matrix Through the SOX4/Wnt/β-Catenin Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Haoyu Wang ◽  
Fei Li ◽  
Wenrui Ban ◽  
Jing Zhang ◽  
Guiqi Zhang
Keyword(s):  
Extracellular Matrix ◽  
Nucleus Pulposus ◽  
Extracellular Vesicles ◽  
Target Genes ◽  
Intervertebral Disk ◽  
Human Bone ◽  
Nucleus Pulposus Cells ◽  
Synthetic Genes ◽  
Downstream Target ◽  
Transcription Factor 4

Objective: Intervertebral disk degeneration (IDD) is a major cause of pain in the back, neck, and radiculus. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) are therapeutic in musculoskeletal degenerative diseases such as IDD. This study explored the effect and functional mechanism of human bone MSCs (hBMSCs)-derived EVs in proliferation and apoptosis of degenerated nucleus pulposus cells (DNPCs) and extracellular matrix (ECM) synthesis.Methods: Extracellular vesicles were isolated from hBMSCs and identified. DNPCs were induced by TNF-α. EVs were incubated with DNPCs for 24h. Internalization of EVs by DNPCs, DNPCs proliferation, apoptosis, and expressions of ECM synthetic genes, degrading genes and miR-129-5p were assessed. Downstream target genes of miR-129-5p were predicted. Target relation between miR-129-5p and SRY-box transcription factor 4 (SOX4) was verified. DNPCs proliferation, apoptosis, and ECM synthesis were measured after treatment with EVs and miR-129-5p inhibitor or SOX4 overexpression. Expressions of SOX4 and Wnt/β-catenin pathway-related proteins were determined.Results: hBMSC-EVs promoted DNPCs proliferation, inhibited apoptosis, increased expressions of ECM synthetic genes, and reduced expressions of ECM degrading genes. hBMSC-EVs carried miR-129-5p into DNPCs. Silencing miR-129-5p in EVs partially inverted the effect of EVs on DNPCs proliferation and ECM synthesis. miR-129-5p targeted SOX4. SOX4 overexpression annulled the effect of EVs on DNPCs proliferation and ECM synthesis. Expressions of Wnt1 and β-catenin were decreased in EVs-treated DNPCs, while silencing miR-129-5p in EVs promoted expressions of Wnt1 and β-catenin.Conclusion: hBMSC-EVs promoted DNPCs proliferation and ECM synthesis by carrying miR-129-5p into DNPCs to target SOX4 and deactivating the Wnt/β-catenin axis.

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