scholarly journals The Role of Oxidative Stress in Intervertebral Disc Degeneration

2022 ◽  
Vol 2022 ◽  
pp. 1-16
Author(s):  
Guoshuai Cao ◽  
Sidong Yang ◽  
Jianye Cao ◽  
Zixuan Tan ◽  
Linyu Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Cellular Damage ◽  
Activation Mechanism ◽  
Discogenic Low Back Pain ◽  
Disc Cells ◽  
Heavy Burden ◽  
Matrix Metabolism

Intervertebral disc degeneration is a very common type of degenerative disease causing severe socioeconomic impact, as well as a major cause of discogenic low back pain and herniated discs, placing a heavy burden on patients and the clinicians who treat them. IDD is known to be associating with a complex process involving in extracellular matrix and cellular damage, and in recent years, there is increasing evidence that oxidative stress is an important activation mechanism of IDD and that reactive oxygen and reactive nitrogen species regulate matrix metabolism, proinflammatory phenotype, autophagy and senescence in intervertebral disc cells, apoptosis, autophagy, and senescence. Despite the tremendous efforts of researchers within the field of IDD pathogenesis, the proven strategies to prevent and treat this disease are still very limited. Up to now, several antioxidants have been proved to be effective for alleviating IDD. In this article, we discussed that oxidative stress accelerates disc degeneration by influencing aging, inflammation, autophagy, and DNA methylation, and summarize some antioxidant therapeutic measures for IDD, indicating that antioxidant therapy for disc degeneration holds excellent promise.

scholarly journals Nrf2 mediated ER-phagy protects against oxidative damage in intervertebral disc degeneration

2021 ◽  
Author(s):  
zhen lin ◽  
libin ni ◽  
cheng teng ◽  
zhao zhang ◽  
xinlei lu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Oxidative Damage ◽  
Er Stress ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Cellular Damage ◽  
Nucleus Pulposus Cells

Intervertebral disc degeneration (IDD) increases the risk of low back pain (LBP). Oxidative stress may induce cellular damage and contribute to various diseases including IDD. Endoplasmic reticulum autophagy (ER-phagy) is a specific type of autophagy, its role in oxidative stress induced damage as well as in IDD is unknown. This study explores the role of ER-phagy in oxidative damage in intervertebral disc nucleus pulposus cells (NPCs), as well as the Nrf2/FAM134B axis in ER-phagy regulation and IDD therapy. We found ER-phagy was decreased in NPCs during oxidative stress; while FAM134B may promote ER-phagy and alleviate oxidative stress induced ER-stress and apoptosis. In addition, the nuclear transcription factor Nrf2 may promote the expression of FAM134B as well as ER-phagy, and suppress ER-stress and apoptosis in NPCs. Furthermore, overexpression of FAM134B and Nrf2 could effectively attenuate the progression of IDD in rats in vivo. These results suggest Nrf2/FAM134B mediated ER-phagy may combat oxidative damage in cells; meanwhile, ER-phagy as well as Nrf2 could be potential therapeutic targets for IDD.

scholarly journals The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Olga Krupkova ◽  
Junichi Handa ◽  
Marian Hlavna ◽  
Juergen Klasen ◽  
Caroline Ospelt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Epigallocatechin Gallate ◽  
Proliferative Capacity ◽  
Suitable Candidate ◽  
Viable Cells ◽  
Natural Polyphenol ◽  
Disc Cells

Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2(totaln=36). Under sublethal conditions, the effects of EGCG on p53-p21 activation, proliferative capacity, and accumulation of senescence-associatedβ-galactosidase were tested. Further, the effects of EGCG on mitochondria depolarization and cell viability were analyzed in lethal oxidative stress. The inhibitor LY249002 was applied to investigate the PI3K/Akt pathway. EGCG inhibited accumulation of senescence-associatedβ-galactosidase but did not affect the loss of proliferative capacity, suggesting that EGCG did not fully neutralize exogenous radicals. Furthermore, EGCG increased the survival of IVD cells in lethal oxidative stress via activation of prosurvival PI3K/Akt and protection of mitochondria. We demonstrated that EGCG not only inhibits inflammation but also can enhance the survival of disc cells in oxidative stress, which makes it a suitable candidate for the development of novel therapies targeting disc degeneration.

Targeting Oxidative Stress with Amobarbital to Prevent Intervertebral Disc Degeneration

2021 ◽  
Author(s):  
Dongrim Seol ◽  
Mitchell C. Coleman ◽  
James A. Martin ◽  
Ino Song ◽  
LR Jaidev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration

scholarly journals Mechanosensitive Ion Channel Piezo1 Activated by Matrix Stiffness Regulates Oxidative Stress-Induced Senescence and Apoptosis in Human Intervertebral Disc Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-13 ◽  
Author(s):  
Bingjin Wang ◽  
Wencan Ke ◽  
Kun Wang ◽  
Gaocai Li ◽  
Liang Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Ion Channel ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Elasticity Modulus ◽  
Mechanosensitive Ion Channel ◽  
Mechanical Transduction ◽  
Crucial Part

Mechanical stimulation plays a crucial part in the development of intervertebral disc degeneration (IDD). Extracellular matrix (ECM) stiffness, which is a crucial mechanical microenvironment of the nucleus pulposus (NP) tissue, contributes to the pathogenesis of IDD. The mechanosensitive ion channel Piezo1 mediates mechanical transduction. This study purposed to investigate the function of Piezo1 in human NP cells under ECM stiffness. The expression of Piezo1 and the ECM elasticity modulus increased in degenerative NP tissues. Stiff ECM activated the Piezo1 channel and increased intracellular Ca2+ levels. Moreover, the activation of Piezo1 increased intracellular reactive oxygen species (ROS) levels and the expression of GRP78 and CHOP, which contribute to oxidative stress and endoplasmic reticulum (ER) stress. Furthermore, stiff ECM aggravated oxidative stress-induced senescence and apoptosis in human NP cells. Piezo1 inhibition alleviated oxidative stress-induced senescence and apoptosis, caused by the increase in ECM stiffness. Finally, Piezo1 silencing ameliorated IDD in an in vivo rat model and decreased the elasticity modulus of rat NP tissues. In conclusion, we identified the mechanosensitive ion channel Piezo1 in human NP cells as a mechanical transduction mediator for stiff ECM stimulation. Our results provide novel insights into the mechanism of mechanical transduction in NP cells, with potential for treating IDD.

scholarly journals Overexpression of BNIP3 in Rat Intervertebral Disc Cells Can Trigger Autophagy-Related Apoptosis

2020 ◽  
Author(s):  
Ting-Sheng Wu ◽  
Shao-Yong Fan ◽  
Bin Zhang ◽  
Zhi-Qiang Tao ◽  
Hong Hua ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Low Back ◽  
Rt Pcr ◽  
Cell Staining ◽  
Apoptotic Protein ◽  
Disc Cells ◽  
Related Proteins ◽  
Western Blotting Assay

Abstract Background: Intervertebral disc degeneration (IDD) is the important cause of low back pain. Excessive apoptosis of intervertebral disc cells is the primary cause of IDD. BNIP3 is a member of Bcl-2 family and is widely involved in cell autophagy and apoptosis. However, the roles and mechanisms of BNIP3 in intervertebral disc cell autophagy and apoptosis are unclear.Results: In this study, the primary rat intervertebral disc cells were prepared and applied to study the effect of BNIP3 overexpression on their autophagy and apoptosis. RT-PCR and western blotting assay showed that BNIP3 overexpression significantly up-regulated the expression of autophagy and pro-apoptotic related proteins, including HIF-1α, Apaf-1, cleaved caspase 3, LC-3 and Beclin-1, while down-regulated the expression of anti-apoptotic protein Bcl-2. Subsequent cell staining detection of autophagy and apoptosis showed that BNIP3 overexpression significantly increased the autophagy and apoptosis of rat intervertebral disc cells. Furthermore, BNIP3 interference assay revealed that the effects of BNIP3 overexpression can be reversed by BNIP3 interference. Conclusions: The above findings suggested that BNIP3 enhanced autophagy of intervertebral disc cells and further triggered the apoptosis of intervertebral disc cells, eventually led to the development of intervertebral disc degeneration.

scholarly journals Restoration of Autophagic Flux Rescues Oxidative Damage and Mitochondrial Dysfunction to Protect against Intervertebral Disc Degeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-27 ◽  
Author(s):  
Liang Kang ◽  
Qian Xiang ◽  
Shengfeng Zhan ◽  
Yu Song ◽  
Kun Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Oxidative Damage ◽  
Mitochondrial Dysfunction ◽  
Disc Degeneration ◽  
Cell Apoptosis ◽  
Intervertebral Disc Degeneration ◽  
Autophagic Flux ◽  
Ecm Degradation

Oxidative stress-induced mitochondrial dysfunction and nucleus pulposus (NP) cell apoptosis play crucial roles in the development of intervertebral disc degeneration (IDD). Increasing studies have shown that interventions targeting impaired autophagic flux can maintain cellular homeostasis by relieving oxidative damage. Here, we investigated the effect of curcumin (CUR), a known autophagy activator, on IDD in vitro and in vivo. CUR suppressed tert-butyl hydroperoxide- (TBHP-) induced oxidative stress and mitochondrial dysfunction and thereby inhibited human NP cell apoptosis, senescence, and ECM degradation. CUR treatment induced autophagy and enhanced autophagic flux in an AMPK/mTOR/ULK1-dependent manner. Notably, CUR alleviated TBHP-induced interruption of autophagosome-lysosome fusion and impairment of lysosomal function and thus contributed to the restoration of blocked autophagic clearance. These protective effects of CUR in TBHP-stimulated human NP cells resembled the effects produced by the autophagy inducer rapamycin, but the effects were partially eliminated by 3-methyladenine- and compound C-mediated inhibition of autophagy initiation or chloroquine-mediated obstruction of autophagic flux. Lastly, CUR also exerted a protective effect against puncture-induced IDD progression in vivo. Our results showed that suppression of excessive ROS production and mitochondrial dysfunction through enhancement of autophagy coupled with restoration of autophagic flux ameliorated TBHP-induced human NP cell apoptosis, senescence, and ECM degradation. Thus, maintenance of the proper functioning of autophagy represents a promising therapeutic strategy for IDD, and CUR might serve as an effective therapeutic agent for IDD.

scholarly journals Protective Effect of Polygonatum sibiricum Polysaccharides on Apoptosis, Inflammation, and Oxidative Stress in Nucleus Pulposus Cells of Rats with the Degeneration of the Intervertebral Disc

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhaohui Zhai ◽  
Zhaoxin Li ◽  
Zhonglei Ji ◽  
Xiaosheng Lu
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Rat Model ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
New Drugs ◽  
Nucleus Pulposus Cells ◽  
And Oxidative Stress

Objective. Polygonatum sibiricum polysaccharide (PSP) has antioxidant activity, immune enhancement, and other biological properties. However, the effect of PSP on intervertebral disc degeneration has not been reported. In this study, we mainly investigated the effect of PSP on the apoptosis, inflammation, and oxidative stress of nucleus pulposus cells (NPCs) during the process of intervertebral disc degeneration. Methods. A rat NPC model induced by H2O2 was constructed. The CCK8 method was used to measure the effects of PSP on the apoptosis of rat NPCs induced by H2O2. The effects on the activity of SOD and content of MDA were also determined. The rat model of intervertebral disc degeneration was treated with PSP for 1 month, and the mRNA expression levels of IL-1β, COX2, iNOS, Col2α1, Col10α1, and MMP3 were measured by qPCR in the tissue of intervertebral disc. NPCs from the degenerated intervertebral discs were separated, and the cell viability was measured by the CCK8 method. The contents of SOD and MDA in NPCs were determined as well. Results. PSP significantly reduced the apoptosis of NPCs induced by H2O2, significantly increased the SOD content, and decreased the content of MDA in H2O2-induced NPCs. The expression level of IL-1β, COX2, and iNOS in the rat model with intervertebral disc degeneration was significantly downregulated after 1 month of PSP treatment. PSP treatment increased the expression of Col2α1 type and significantly decreased the expression of Col10α1 type collagen and MMP3 in rats with disc degeneration. PSP treatment significantly reduced NPC apoptosis and increased its SOD content and reduced MDA content, which is consistent with the results from cell-level experiments. Conclusion. PSP can effectively reduce the apoptosis, inflammation, and oxidative stress of H2O2-induced NPCs in rats with intervertebral disc degeneration and mitigate the progression of intervertebral disc degeneration, which has the potential to be developed as new drugs for the treatment of intervertebral disc degeneration.

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