The circadian rhythm in intervertebral disc degeneration: an autophagy connection

Zhang, Tai-Wei; Li, Ze-Fang; Dong, Jian; Jiang, Libo

doi:10.1038/s12276-019-0372-6

Cited by 32 publications

(14 citation statements)

References 106 publications

(151 reference statements)

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“…Autophagy is a catabolic process aimed at recycling cellular components and damaged organelles in response to diverse conditions of stress [ 15 ]. In recent years, an increasing number of studies have shown that autophagy plays an important role in the process of IDD, and most scholars believe that abnormal regulation of autophagy levels and abnormal nutrients in the intervertebral disc are important mechanisms leading to IDD [ 16 , 17 ]. Interestingly, a recent study found that the disc degeneration is caused by an imbalance between autophagy and apoptosis in NP cells [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

CircRNA RERE Promotes the Oxidative Stress-Induced Apoptosis and Autophagy of Nucleus Pulposus Cells through the miR-299-5p/Galectin-3 Axis

Wang¹,

Zhou

Luo³

et al. 2021

Journal of Healthcare Engineering

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Intervertebral disc degeneration (IDD) is widely accepted as a cause of low back pain and related degenerative musculoskeletal disorders. Nucleus pulposus (NP) cell loss is closely related to IDD progression. Thus, investigating the specifically targeted therapeutic agents against NP cell loss depends on understanding the molecular mechanisms. In this study, human NP cells were treated with hydrogen peroxide (H2O2). Cell viability was assessed by using the Cell Counting Kit-8 (CCK-8) kit. The expression of circRNA arginine-glutamic acid dipeptide repeats (hsa_circ_RERE) and miR-299-5p was analyzed by real-time quantitative PCR. Western blot analysis was used to assess the protein expression levels. The autophagy levels in NP cells were detected by using an electronic microscope, LC3B protein immunofluorescence, and western blot. The apoptosis levels of NP cells were detected by flow cytometry and western blot. Dual-luciferase reporter assay analyzed the miR-299-5p bound to circ_RERE and galectin-3. Our results revealed that H2O2 significantly inhibited the viability of NP cells, promoted apoptosis and autophagy, and upregulated galectin-3 expression. miR-299-5p was reduced in IDD and H2O2-induced NP cells. The overexpression of miR-299-5p promoted cell viability and attenuated apoptosis and autophagy under H2O2 treatment. Besides, circ_RERE was upregulated in IDD and H2O2-induced NP cells. However, knockdown of circ_RERE reversed the effects of miR-299-5p overexpression on cell viability, apoptosis, and autophagy in NP cells. We propose that circ_RERE promotes the H2O2-induced apoptosis and autophagy of NP cells through the miR-299-5p/galectin-3 axis and may provide a new target for the clinical treatment of IDD.

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Section: Introductionmentioning

confidence: 99%

CircRNA RERE Promotes the Oxidative Stress-Induced Apoptosis and Autophagy of Nucleus Pulposus Cells through the miR-299-5p/Galectin-3 Axis

Wang¹,

Zhou

Luo³

et al. 2021

Journal of Healthcare Engineering

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“…Autophagy plays a role in determining the lifespan of many organisms and has been implicated in various pathologic processes 17 . Autophagy maintains homeostatic functions such as protein and organelle turnover and is upregulated during starvation, periods of high bioenergetic demand, growth factor withdrawal, oxidative stress, protein aggregation, and infection 18 …”

Section: Introductionmentioning

confidence: 99%

Decorin inhibits nucleus pulposus apoptosis by matrix‐induced autophagy via the mTOR pathway

Zhang

Ding

et al. 2020

Journal Orthopaedic Research

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Decorin (Dcn) is a member of the class I small leucine‐rich proteoglycans, whose expression in the nucleus pulposus (NP) of intervertebral discs (IVDs) has been shown to increase with aging in humans and sheep. Dcn induces autophagy in endothelial cells; however, its precise role in NP and IVD degeneration during aging is not well understood. We addressed this question in the present study by treating rat nucleus pulposus cells (NPCs) with different concentrations of Dcn. The Western blot analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling assay results showed that Dcn treatment induced autophagy and decreased apoptosis caused by interleukin (IL)‐1β application. This effect was dependent on the protein kinase B/mechanistic target of rapamycin (mTOR)/p70 S6 kinase signaling. Dcn treatment also decreased the expression of matrix metalloproteinase‐3 and ‐13 and decreased the IL‐1β‐induced attenuation of collagen type II and aggrecan levels. The role of Dcn in stimulating autophagy was further supported by the fact that the observed effects were abrogated by knocking down autophagy‐related protein 7 with Atg7 small interfering RNA. Thus, Dcn protects NPCs in IVDs from IL‐1β‐induced apoptosis and degeneration by promoting autophagy through mTOR signaling.

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“…Autophagy is essentially a lysosome-mediated intracellular catabolic process in which dysfunctional cytoplasmic macromolecules and damaged organelles can be degraded and recycled in response to external stimuli to increased metabolism. Previous studies have confirmed the relationship between autophagy and IVDD [ 33 ]. Low levels of autophagy are found in healthy intervertebral discs.…”

Section: Discussionmentioning

confidence: 61%

Quercetin Alleviates Intervertebral Disc Degeneration by Modulating p38 MAPK-Mediated Autophagy

Zhang

Abulizi

et al. 2021

BioMed Research International

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Intervertebral disc degeneration (IVDD) is a degenerative and chronic spinal disorder often associated with the older population. Oxidative stress is a major pathogenic factor of aging that results in the apoptosis of nucleus pulposus cells (NPCs) and extracellular matrix (ECM) degradation. Quercetin (QUE), a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, has been studied in research on degenerative diseases. However, the potential effects and mechanisms of action of QUE on IVDD remain unclear. In this study, the effects of QUE on antiapoptosis and ECM metabolism were firstly investigated in TBHP-treated NPCs. Meanwhile, the autophagy inhibitor, 3-MA, and p38 MAPK inhibitor, SB203580, were used in subsequent TBHP-induced NPC experiments to determine whether QUE exerted its protective effects through autophagy and the p38 MAPK/mTOR signaling pathway. Finally, the therapeutic effects of QUE were confirmed in vivo using a rat tail needle puncture-induced model of IVDD. We found that QUE treatment significantly alleviated oxidative stress-decreased cell viability and intracellular ROS levels in NPCs treated with TBHP. Furthermore, treatment with QUE led to a decrease in apoptosis as measured by decreased Bax and increased Bcl-2 expression and PE/7-AAD flow cytometry analysis. QUE also promoted ECM stability as measured by increased collagen II and aggrecan and decreased MMP13 levels. Our results also showed that QUE promoted the expression of autophagy markers beclin-1, LC3-II/I, and decreased p62. Inhibition of autophagy by inhibitor 3-MA may partially reverse the protective effect of QUE on apoptosis and ECM degeneration, indicating that autophagy was involved in the protective effect of QUE in NPCs. Further study confirmed that QUE partially inhibited the p38 MAPK signaling pathway and inhibition of p38 MAPK by SB203580 activated autophagy, indicating that QUE protected NPCs against apoptosis and prevented ECM degeneration via the p38 MAPK-autophagy pathway. Finally, using a rat tail puncture-induced model of IVDD, we confirmed that QUE had a protective effect against IVDD. Our results suggest that QUE could prevent IVDD by modulating p38 MAPK-mediated autophagy and, therefore, is a potential therapeutic strategy in the treatment of IVDD.

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The circadian rhythm in intervertebral disc degeneration: an autophagy connection

Cited by 32 publications

References 106 publications

CircRNA RERE Promotes the Oxidative Stress-Induced Apoptosis and Autophagy of Nucleus Pulposus Cells through the miR-299-5p/Galectin-3 Axis

CircRNA RERE Promotes the Oxidative Stress-Induced Apoptosis and Autophagy of Nucleus Pulposus Cells through the miR-299-5p/Galectin-3 Axis

Decorin inhibits nucleus pulposus apoptosis by matrix‐induced autophagy via the mTOR pathway

Quercetin Alleviates Intervertebral Disc Degeneration by Modulating p38 MAPK-Mediated Autophagy

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