scholarly journals Arginase II Promotes Intervertebral Disc Degeneration Through Exacerbating Senescence and Apoptosis Caused by Oxidative Stress and Inflammation via the NF-κB Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Fudong Li ◽  
Xiaofei Sun ◽  
Bing Zheng ◽  
Kaiqiang Sun ◽  
Jian Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Therapeutic Strategy ◽  
Opposite Effect ◽  
Nucleus Pulposus Cells ◽  
Cellular Processes ◽  
Arginase Ii

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which imposes massive clinical and socioeconomic burdens. Previous studies have demonstrated that oxidative stress and inflammation-induced senescence and apoptosis of nucleus pulposus cells (NPCs) are the main cellular processes that cause IDD. Arginase II (ARG2), an enzyme involved in a variety of pathological processes, including cellular senescence, apoptosis, oxidative stress, and inflammation, has been shown to promote degeneration in several degenerative diseases, including osteoarticular diseases. Based on previous studies, we hypothesized that ARG2 deficiency might be conducive to the treatment of IDD by inhibiting the dyshomeostasis of the extracellular matrix (ECM), and the oxidative stress and inflammatory response-induced senescence and apoptosis via NF-κB. In this study, we found that ARG2 deficiency inhibited senescence and apoptosis of NPCs, and degeneration of the ECM induced by oxidative stress and the inflammatory response. Similar results were found with the selective NF-κB pathway inhibitor JSH-23. In contrast, overexpression of ARG2 had the opposite effect. Taken together, our results suggest that ARG2 deficiency prevents IDD via NF-κB, and may therefore, be a potential therapeutic strategy for IDD.

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 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.

scholarly journals Circ_0004354 might compete with circ_0040039 to induce NPCs death and inflammatory response by targeting miR-345-3p-FAF1/TP73 axis in intervertebral disc degeneration

2022 ◽  
Vol 2022 ◽  
pp. 1-21
Author(s):  
Yongjin Li ◽  
Xiaojing Wu ◽  
Jianhua Li ◽  
Lilong Du ◽  
Xuke Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Pathological Process ◽  
Circular Rnas ◽  
Nucleus Pulposus Cells ◽  
Promising Therapeutic Target ◽  
Pathological Mechanism ◽  
Ecm Degradation

The abnormal function of nucleus pulposus cells (NPCs) plays a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Recent studies have demonstrated that circular RNAs (circRNAs) are involved in the pathological process of IVDD by regulating NPCs’ function. Nevertheless, the investigation on circRNA-circRNA interaction has not yet been reported. Here, we identified the top upregulated circ_0040039 and circ_0004354 in IVDD, derived from the syntrophin beta 2 gene but had different degrees of biological functions. Accumulating studies have reported PANoptosis is composed of apoptosis, pyroptosis, and necroptosis. Based on this, we think there should be a new pro-inflammatory cell death PAoptosis in the form of apoptosis and pyroptosis. Circ_0004354 might compete with circ_0040039 to induce the development of IVDD by modulating miR-345-3p-FAF1/TP73 axis-mediated PAoptosis, inflammatory response, growth inhibition, and ECM degradation of NPCs. Thus, these findings offer a novel insight into the circRNAs-mediated posttranscriptional regulatory network in IVDD, contributing to further clarification of the pathological mechanism of IVDD to develop a promising therapeutic target for IVDD diseases.

Therapeutic Potential of Naringin for Intervertebral Disc Degeneration: Involvement of Autophagy Against Oxidative Stress-Induced Apoptosis in Nucleus Pulposus Cells

2018 ◽  
Vol 46 (07) ◽  
pp. 1561-1580 ◽  
Author(s):  
Zengjie Zhang ◽  
Chenggui Wang ◽  
Jialiang Lin ◽  
Haiming Jin ◽  
Ke Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Therapeutic Potential ◽  
Nucleus Pulposus Cells ◽  
Induced Apoptosis

Intervertebral disc degeneration (IDD) is a major cause of lower back pain, but few efficacious medicines have been developed for IDD. Increased nucleus pulposus cells apoptosis is a dominant pathogenesis of IDD and is considered a therapeutic target. Previously, our group proved that autophagy may protect nucleus pulposus cells against apoptosis. As one of the major bioflavonoids of citrus, naringin activates autophagy. Therefore, we hypothesize that naringin may have therapeutic potential for IDD by activating autophagy in nucleus pulposus cells. In this study, we evaluated the effects of naringin on TBHP-induced oxidative stress in nucleus pulposus cells in vitro as well as in puncture-induced rat IDD model in vivo. Our results showed that naringin could reduce the incidence of oxidative stress-induced apoptosis in nucleus pulposus cells and promoted the expression of autophagy markers LC3-II/I and beclin-1. Meanwhile, inhibition of autophagy by 3-MA may partially reverse the anti-apoptotic effect of naringin, indicating that autophagy was involved in the protective effect of naringin in nucleus pulposus cells. Further study showed that autophagy regulation of naringin may be related to AMPK signaling. Also, we found that naringin treatment can regulate the expression of collagen II, aggrecan and Mmp13 to sustain the extracellular matrix. Furthermore, our in vivo study showed that naringin can ameliorate IDD in puncture-induced rat model. In conclusion, our study suggests that naringin can protect nucleus pulposus cells against apoptosis and ameliorate IDD in vivo, the mechanism may relate to its autophagy regulation.

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