scholarly journals Mitochondrial quality control in intervertebral disc degeneration

2021 ◽  
Author(s):  
Yu Song ◽  
Saideng Lu ◽  
Wen Geng ◽  
Xiaobo Feng ◽  
Rongjin Luo ◽  
...  
Keyword(s):  
Quality Control ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Intervertebral Discs ◽  
Mitochondrial Quality Control

AbstractIntervertebral disc degeneration (IDD) is a common and early-onset pathogenesis in the human lifespan that can increase the risk of low back pain. More clarification of the molecular mechanisms associated with the onset and progression of IDD is likely to help establish novel preventive and therapeutic strategies. Recently, mitochondria have been increasingly recognized as participants in regulating glycolytic metabolism, which has historically been regarded as the main metabolic pathway in intervertebral discs due to their avascular properties. Indeed, mitochondrial structural and functional disruption has been observed in degenerated nucleus pulposus (NP) cells and intervertebral discs. Multilevel and well-orchestrated strategies, namely, mitochondrial quality control (MQC), are involved in the maintenance of mitochondrial integrity, mitochondrial proteostasis, the mitochondrial antioxidant system, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis. Here, we address the key evidence and current knowledge of the role of mitochondrial function in the IDD process and consider how MQC strategies contribute to the protective and detrimental properties of mitochondria in NP cell function. The relevant potential therapeutic treatments targeting MQC for IDD intervention are also summarized. Further clarification of the functional and synergistic mechanisms among MQC mechanisms may provide useful clues for use in developing novel IDD treatments.

scholarly journals Adipocyte-Mineralocorticoid Receptor Alters Mitochondrial Quality Control Leading to Mitochondrial Dysfunction and Senescence of Visceral Adipose Tissue

2021 ◽  
Vol 22 (6) ◽  
pp. 2881
Author(s):  
Clara Lefranc ◽  
Malou Friederich-Persson ◽  
Fabienne Foufelle ◽  
Aurélie Nguyen Dinh Cat ◽  
Frédéric Jaisser
Keyword(s):  
Quality Control ◽  
Adipose Tissue ◽  
Mitochondrial Dysfunction ◽  
Cellular Senescence ◽  
Mineralocorticoid Receptor ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Oxidative Stress ◽  
Specific Effects

Mineralocorticoid receptor (MR) expression is increased in the adipose tissue (AT) of obese patients and animals. We previously demonstrated that adipocyte-MR overexpression in mice (Adipo-MROE mice) is associated with metabolic alterations. Moreover, we showed that MR regulates mitochondrial dysfunction and cellular senescence in the visceral AT of obese db/db mice. Our hypothesis is that adipocyte-MR overactivation triggers mitochondrial dysfunction and cellular senescence, through increased mitochondrial oxidative stress (OS). Using the Adipo-MROE mice with conditional adipocyte-MR expression, we evaluated the specific effects of adipocyte-MR on global and mitochondrial OS, as well as on OS-induced damage. Mitochondrial function was assessed by high throughput respirometry. Molecular mechanisms were probed in AT focusing on mitochondrial quality control and senescence markers. Adipo-MROE mice exhibited increased mitochondrial OS and altered mitochondrial respiration, associated with reduced biogenesis and increased fission. This was associated with OS-induced DNA-damage and AT premature senescence. In conclusion, targeted adipocyte-MR overexpression leads to an imbalance in mitochondrial dynamics and regeneration, to mitochondrial dysfunction and to ageing in visceral AT. These data bring new insights into the MR-dependent AT dysfunction in obesity.

scholarly journals The Loss of Mitochondrial Quality Control in Diabetic Kidney Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenni Dai ◽  
Hengcheng Lu ◽  
Yinyin Chen ◽  
Danyi Yang ◽  
Lin Sun ◽  
...  
Keyword(s):  
Quality Control ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Protein Quality ◽  
Current Knowledge ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Protein ◽  
Eukaryotic Cell ◽  
Mitochondrial Quality Control ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is the predominant complication of diabetes mellitus (DM) and the leading cause of chronic kidney disease and end-stage renal disease worldwide, which are major risk factors for death. The pathogenesis of DKD is very complicated, including inflammation, autophagy impairment, oxidative stress, and so on. Recently, accumulating evidence suggests that the loss of mitochondrial quality control exerts critical roles in the progression of DKD. Mitochondria are essential for eukaryotic cell viability but are extremely vulnerable to damage. The mechanisms of mitochondrial quality control act at the molecular level and the organelle level, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control. In this review, we summarize current knowledge of the role of disturbances in mitochondrial quality control in the pathogenesis of DKD and provide potential insights to explore how to delay the onset and development of DKD.

scholarly journals Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF-α and Smad Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shaoyi Wang ◽  
Jianlu Wei ◽  
Jie Shi ◽  
Qiting He ◽  
Xiaocong Zhou ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Intervertebral Discs ◽  
Inflammatory Factors ◽  
Wild Type ◽  
Tnf Α

Background. Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases. Objectives. The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression. Methods. We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting. Results. In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF-α-induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65. Conclusion. Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF-α response and Smad pathway activity and ultimately delayed 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 Circular RNAs in nucleus pulposus cell function and intervertebral disc degeneration

2019 ◽  
Vol 52 (6) ◽  
Author(s):  
Zheng Li ◽  
Xin Chen ◽  
Derong Xu ◽  
Shugang Li ◽  
Matthew T. V. Chan ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Cell Function ◽  
Nucleus Pulposus Cell ◽  
Circular Rnas

scholarly journals Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-κB Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yazhou Lin ◽  
Guoqing Tang ◽  
Yucheng Jiao ◽  
Ye Yuan ◽  
Yuehuan Zheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Propionibacterium Acnes ◽  
Intervertebral Discs ◽  
Cox 2 ◽  
Underlying Mechanisms

Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE2) in human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed increased iNOS/NO and COX-2/PGE2 activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE2 expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE2 was essential to the occurrence of P. acnes-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE2 activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE2 expressions via a reactive oxygen species- (ROS-) dependent NF-κB cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE2 expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE2 activation via the ROS-dependent NF-κB pathway is likely responsible for the pathology of IVDD.

scholarly journals Mangiferin Alleviates Mitochondrial ROS in Nucleus Pulposus Cells and Protects against Intervertebral Disc Degeneration via Suppression of NF-κB Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-27
Author(s):  
Haichao Yu ◽  
Guowei Hou ◽  
Jiankang Cao ◽  
Yanyu Yin ◽  
Yunpeng Zhao ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Nucleus Pulposus Cells ◽  
Mitochondrial Ros ◽  
Tnf Α

Intervertebral disc degeneration (IVDD), one of the most common clinical diseases worldwide, causes disc herniation and sciatica. Recent studies have identified the involvement of mitochondrial dysfunction, inflammatory responses, and extracellular matrix degradation in IVDD. Mangiferin is known to protect against various diseases by inhibiting oxidative stress, suppressing inflammation reaction, and relieving mitochondrial dysfunction. Whether mangiferin can alleviate IVDD remains to be elucidated. In the present study, human nucleus pulposus cells (HNPCs) and mouse intervertebral discs were cultured and stimulated with TNF-α, with or without treatment of mangiferin. Moreover, we established a rat needle puncture model and injected mangiferin into the intervertebral discs to verify its protective effect on IVDD. Furthermore, the activity of the NF-κB signaling pathway was tested in vitro. Our results indicated that mangiferin alleviated the inflammatory response and reversed the loss of major intervertebral disc components. Besides, mangiferin reduced reactive oxygen species production, ameliorated mitochondrial damage, and decreased the expression of apoptosis-related parameters in stimulation of TNF-α. In addition, mangiferin antagonized the activation of the NF-κB signaling pathway induced by TNF-α. Collectively, mangiferin antagonized mitochondrial ROS in NP cells and protected against IVDD by suppressing the activation of the NF-κB signaling pathway, which might provide a potential therapeutic instrument for IVDD.

scholarly journals Mechanism of Long Noncoding RNA HOTAIR in Nucleus Pulposus Cell Autophagy and Apoptosis in Intervertebral Disc Degeneration

2022 ◽  
Vol 2022 ◽  
pp. 1-18
Author(s):  
Shujun Zhang ◽  
Sheng Song ◽  
Wei Cui ◽  
Xueguang Liu ◽  
Zhenzhong Sun
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
Luciferase Reporter ◽  
Blue Staining ◽  
Tunel Staining ◽  
Lncrna Hotair

Objective. Intervertebral disc degeneration (IDD) contributes to cervical and lumbar diseases. Long noncoding RNAs (lncRNAs) are implicated in IDD. This study explored the mechanism of lncRNA HOTAIR in IDD. Methods. Normal and degenerative nucleus pulposus (NP) cells were isolated from NP tissues obtained in intervertebral disc surgery. Cell morphology was observed by immunocytochemistry staining and toluidine blue staining. NP cell markers were detected by RT-qPCR. Proliferation was detected by MTT assay. Autophagy-related proteins were detected by Western blot. Autophagosome was observed by monodansylcadaverine fluorescence staining. Apoptosis was detected by TUNEL staining and flow cytometry. si-HOTAIR and/or miR-148a inhibitor was introduced into degenerative NP cells. Binding relationships among HOTAIR, miR-148a, and PTEN were predicted and verified by dual-luciferase reporter assay and RNA pull-down. Finally, IDD rat models were established. Rat caudal intervertebral discs were assessed by HE staining. Expressions of HOTAIR, miR-148a, and PTEN were determined by RT-qPCR. Results. HOTAIR was highly expressed in degenerative NP cells p < 0.05 . si-HOTAIR inhibited degenerative NP cell apoptosis and autophagy p < 0.05 . HOTAIR upregulated PTEN as a sponge of miR-148a. miR-148a was poorly expressed in degenerative NP cells. miR-148a deficiency partially reversed the inhibition of si-HOTAIR on degenerative NP cell autophagy and apoptosis (all p < 0.05 ). In vivo assay confirmed that si-HOTAIR impeded autophagy and apoptosis in intervertebral disc tissues, thus improving pathological injury in IDD rats (all p < 0.05 ). Conclusion. LncRNA HOTAIR promoted NP cell autophagy and apoptosis via promoting PTEN expression as a ceRNA of miR-148a in IDD.

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