scholarly journals Karacoline, identified by network pharmacology, reduces degradation of the extracellular matrix in intervertebral disc degeneration via the NF-κB signaling pathway

2020 ◽  
Vol 10 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Xiaoli Zhou ◽  
Yingying Hong ◽  
Yulin Zhan
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Network Pharmacology

Stachydrine ameliorates the progression of intervertebral disc degeneration via the PI3K/Akt/NF-κB signaling pathway: in vitro and in vivo studies

2020 ◽  
Vol 11 (12) ◽  
pp. 10864-10875
Author(s):  
Zhenxuan Shao ◽  
Jiajie Lu ◽  
Chenxi Zhang ◽  
Guoling Zeng ◽  
Boda Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Inflammatory Responses ◽  
In Vivo Studies ◽  
Matrix Degradation

Stachydrine ameliorates inflammatory responses and extracellular matrix degradation, via the PI3K/Akt/NF-κB signalling pathway in the progression of intervertebral disc degeneration.

scholarly journals Pharmacological Mechanism of Danggui-Sini Formula for Intervertebral Disc Degeneration: A Network Pharmacology Study

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Longjie Wang ◽  
Jialiang Lin ◽  
Weishi Li
Keyword(s):  
Molecular Docking ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Biological Mechanism ◽  
Core Genes

Background. Intervertebral disc degeneration (IVDD) is the most significant cause of low back pain, the sixth-largest disease burden globally, and the leading cause of disability. This study is aimed at investigating the molecular biological mechanism of Danggui-Sini formula (DSF) mediated IVDD treatment. Methods. A potential gene set for DSF treatment of IVDD was identified through TCMSP, UniProt, and five disease gene databases. A protein interaction network of common targets between DSF and IVDD was established by using the STRING database. GO and KEGG enrichment analyses were performed using the R platform to discover the potential mechanism. Moreover, AutoDock Vina was used to verify molecular docking and calculate the binding energy. Results. A total of 119 active ingredients and 136 common genes were identified, including 10 core genes (AKT1, IL6, ALB, TNF, VEGFA, TP53, MAPK3, CASP3, JUN, and EGF). Enrichment analysis results showed that the therapeutic targets of DSF for diseases mainly focused on the AGE-RAGE signaling pathway involved in diabetic complications, IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, apoptosis, cellular senescence, PI3K-Akt signaling pathway, and FoxO signaling pathway. These biological processes are induced mainly in response to oxidative stress and reactive oxygen species and the regulation of apoptotic signaling pathways. Molecular docking showed that there was a stable affinity between the core genes and the key components. Conclusions. The combination of network pharmacology and molecular docking provides a practical way to analyze the molecular biological mechanism of DSF-mediated IVDD treatment, which confirms the “multicomponent, multitarget and multipathway” characteristics of DSF and provides an essential theoretical basis for clinical practice.

scholarly journals The mechanism of Bushen Huoxue decoction in treating intervertebral disc degeneration based on network pharmacology

2021 ◽  
Vol 10 (3) ◽  
pp. 49-49
Author(s):  
Shuai-Hua Feng ◽  
Fang Xie ◽  
Hong-Yan Yao ◽  
Guan-Bao Wu ◽  
Xiang-Yun Sun ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Network Pharmacology ◽  
Bushen Huoxue Decoction

scholarly journals JAG2/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Long ◽  
Xiaobo Wang ◽  
Xianfa Du ◽  
Hehai Pan ◽  
Jianru Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Intervertebral Disc ◽  
Notch Signaling ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Caspase 8 ◽  
Tnf Α ◽  
Intradiscal Injection

Abstract Background Intervertebral disc degeneration (IVDD)-related disorders are the major causes of low back pain. A previous study suggested that Notch activation serves as a protective mechanism and is a part of the compensatory response that maintains the necessary resident nucleus pulposus (NP) cell proliferation to replace lost or non-functional cells. However, the exact mechanism remains to be determined. In this study, we aimed to investigate the role of JAG2/Notch2 in NP cell proliferation and apoptosis. Methods Recombinant JAG2 or Notch2, Hes1, and Hey2 siRNAs were used to activate or inhibit Notch signaling. Cell proliferation, apoptosis, cell cycle regulatory factors, and pathways associated with Notch-mediated proliferation were examined. In vivo experiments involving an intradiscal injection of Sprague-Dawley rats were performed. Results Recombinant JAG2 induced Notch2 and Hes1/Hey2 expression together with NP cell proliferation. Downregulation of Notch2/Hes1/Hey2 induced G0/G1 phase cell cycle arrest in NP cells. Moreover, Notch2 mediated NP cell proliferation by regulating cyclin D1 and by activating PI3K/Akt and Wnt/β-catenin signaling. Furthermore, Notch signaling inhibited TNF-α-promoted NP cell apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Finally, we found that intradiscal injection of JAG2 alleviated IVDD and that sh-Notch2 aggravated IVDD in a rat model. These results indicated that JAG2/Notch2 inhibited IVDD by modulating cell proliferation, apoptosis, and extracellular matrix. The JAG2/Notch2 axis regulated NP cell proliferation via PI3K/Akt and Wnt/β-catenin signaling and inhibited TNF-α-induced apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Conclusions The current and previous results shed light on the therapeutic implications of targeting the JAG2/Notch2 axis to inhibit or reverse IVDD.

scholarly journals Melatonin Protects Intervertebral Disc from Degeneration by Improving Cell Survival and Function via Activation of the ERK1/2 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Jun Ge ◽  
Quan Zhou ◽  
Junjie Niu ◽  
Yingjie Wang ◽  
Qi Yan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Nucleus Pulposus Cell ◽  
Cell Physiology ◽  
Cell Degeneration

Melatonin, a neuroendocrine hormone secreted by the pineal body, has a positive effect on intervertebral disc degeneration. The present study is aimed at investigating the biological role of melatonin in intervertebral disc degeneration and its underlying mechanism. A human nucleus pulposus cell (NPC) line was exposed to melatonin at different concentrations. Cell proliferation was measured by CCK-8 assay. Cell cycle and apoptosis were analyzed by flow cytometry. Western blot was performed to measure the protein expression of indicated genes. A rabbit model of intervertebral disc degeneration was established to detect the role and mechanism of melatonin on intervertebral disc degeneration. Our study showed that melatonin promoted NPC viability and inhibited cell arrest. Furthermore, melatonin treatment led to the upregulation of collagen II and aggrecan and downregulation of collagen X. Moreover, melatonin significantly elevated the activity of the ERK signaling pathway. Inhibition of the ERK1/2 signals reversed the role of melatonin in the regulation of NPCs both in vitro and in vivo. Melatonin increased NPC viability through inhibition of cell cycle arrest and apoptosis. Moreover, melatonin promoted the secretion of functional factors influencing the nucleus pulposus cell physiology and retarded cell degeneration. Our results suggest that melatonin activated the ERK1/2 signaling pathway, thereby affecting the biological properties of the intervertebral disc degeneration.

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