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

Abstract Background The HIF-1α/Notch signaling pathway has been shown to regulate proliferation, apoptosis, and metabolism in the intervertebral disc (IVD). The NP is an important structure adjacent to the disc. However, the roles of HIF1α and Notch signaling pathways in NP cells of patients with different Modic changes (MCs) are unclear. The purpose of this research was to assess the expression and association of HIF-1α and components of the Notch pathway in nucleus pulposus (NP) tissue of patients with various MCs. Methods Eighty-five surgical NP tissue samples were obtained from patients undergoing microdiscectomy procedures for the treatment of low back and root pain caused by prolapse of the IVD. The NP tissues were divided into four groups based on the adjacent endplate degeneration: MC I, II, III, and negative MC groups. The expression of HIF-1α and Notch-related components were measured and compared. Results The expression of HIF-1α, Notch1, and Notch2 were gradually increased in the MC I and MC II groups compared with that of the negative MC group. Meanwhile, HIF-1α and Notch-related components were rarely detected in MC III group. Conclusions The expression of HIF-1α/Notch is increased in the NP cells of patients with MC I and MC II. Application of the association between HIF-1α/Notch signaling pathway could be promising target for clinical diagnosis and treatment of disc degeneration in MC patients.

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LncRNA FAM83H‐AS1 induces nucleus pulposus cell growth via targeting the Notch signaling pathway

Journal of Cellular Physiology ◽

10.1002/jcp.28780 ◽

2019 ◽

Vol 234 (12) ◽

pp. 22163-22171 ◽

Cited By ~ 5

Author(s):

Rong Wei ◽

Yuxuan Chen ◽

Zheyuan Zhao ◽

Qiuhan Gu ◽

Junlong Wu

Keyword(s):

Cell Growth ◽

Notch Signaling ◽

Signaling Pathway ◽

Nucleus Pulposus ◽

Nucleus Pulposus Cell ◽

Notch Signaling Pathway

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

Cellular Physiology and Biochemistry ◽

10.1159/000494650 ◽

2018 ◽

Vol 50 (4) ◽

pp. 1510-1521 ◽

Cited By ~ 1

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.

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

Food & Function ◽

10.1039/d0fo03353g ◽

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.

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