Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc

Chen, Ke; Lv, Xiaohua; Li, Wei; Yu, Fei; Lin, Jianjing; Ma, Junxuan; Xiao, Deming

doi:10.1155/2017/4041768

Cited by 37 publications

(30 citation statements)

References 50 publications

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“…Autophagy is a process used to degrade useless proteins or organelles to maintain cellular functions (41). Increasing evidence has indicated that moderate autophagy exhibits a protective function against cellular pathologies, including IDD (42). In addition, a specific study revealed that autophagy-associated genes were downregulated in IDD tissues compared with healthy tissues, including Beclin-1 (28).…”

Section: Discussionmentioning

confidence: 99%

β‑ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration

Wen

et al. 2019

Mol Med Report

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Increasing cell apoptosis is one of the major causes of intervertebral disc degeneration (IDD). β-ecdysterone has been demonstrated to protect PC12 cells against neurotoxicity. A previous study revealed that β-ecdysterone may be involved in the regulation of autophagy in osteoblasts. Therefore, we hypothesized that β-ecdysterone may possess therapeutic effects on IDD via autophagy stimulation. The effect of β-ecdysterone on IDD was explored by in vitro experiments. The results demonstrated that β-ecdysterone attenuated the apoptosis induced by tert-butyl hydroperoxide via promoting autophagy in nucleus pulposus cells. Beclin-1, an indispensable protein for the stimulation of autophagy, is upregulated and stabilized by β-ecdysterone in a dose-and time-dependent manner in nucleus pulposus cells. Inhibition of autophagy with 3-methyladenine partially abrogated the protective function of β-ecdysterone against apoptosis of nucleus pulposus cells, indicating that autophagy participated in the protective effect of β-ecdysterone on IDD. Additionally, β-ecdysterone promoted the expression of anabolic genes while inhibiting the expression of catabolic genes in nucleus pulposus cells. Collectively, the present study demonstrated that β-ecdysterone may protect nucleus pulposus cells against apoptosis by autophagy stimulation and ameliorate disc degeneration, which indicates that β-ecdysterone may be a potential therapeutic agent for IDD.

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Section: Discussionmentioning

confidence: 99%

β‑ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration

Wen

et al. 2019

Mol Med Report

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“…Autophagy has been shown to have a positive effect on cell survival by mediating the selective removal of damaged cell components [54,67]. In addition, autophagy has been shown to instigate a protective effect against oxidative damage to endplate chondrocytes in intervertebral discs as the inhibition of autophagy increased apoptosis [68]. Corresponding with our results, glucosamine was found to activate autophagy in NP cells in a dose-dependent manner and attenuated the decrease of aggrecan to prevent the apoptosis of NP cells induced by IL-1β, whereas 3-MA partly reversed these effects [69].…”

Section: Discussionmentioning

confidence: 99%

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Shi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in an outer layer known as the annulus fibrosus. ECM metabolic disorders result in loss of boundary between the annulus fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such as interleukin (IL)-1β, mediate the progression of IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) and is known to be induced by IL-1β. APO866 is an inhibitor of NAD biosynthesis and is involved in autophagy. LC3 (microtubule-associated protein 1 light chain 3) is a key regulator of autophagy and is used as an indicator of increased autophagy. Herein, we investigate the role of APO866 in regulating autophagy in NP cells and IL-1β mediated NP cell degeneration and apoptosis. Methods: NP cells were extracted from IDD tissues and cultured in DMEM/F12 medium. Nampt was induced by different concentrations of IL-1β (0, 0.5, 1, 5, 10 ng/mL) for 24 h or NP cells were treated with 10 ng/mL IL-1β for 0, 6, 12, 48 h. QRT-PCR and western blots were used to detect Nampt and ECM-related protein expression in NP tissue of patients with IDD and in NP cells. Confocal analysis was used to detect membrane-bound LC3, Aggrecan, and Collagen II. Results: Nampt is expressed in NP tissue at higher levels in severe grades of IDD (Grade IV and V) compared with low grades (Grade II and III). In NP cells, 10 ng/mL IL-1β induced Nampt expression for 48 h, increased expression of the degradative-associated proteins, ADAMTS4/5 and MMP-3/13, and decreased expression of ECM-related proteins, Aggrecan and Collagen II. However, the Nampt inhibitor APO866 blocked IL-1β induction, and the knockdown of Nampt expression increased the expression of ECM proteins that were inhibited by IL-1β. Moreover, evidence provided by the autophagic markers LC3 and Beclin-1 indicated that APO866 induced NP cell autophagy. Furthermore, although APO866 inhibited the downregulated expression of ECM-related proteins by IL-1β, this function was blocked by autophagy inhibitor, 3-methyladenine. Conclusion: APO866 protects NP cells and induces autophagy by inhibiting IL-1β-induced NP cell degeneration and apoptosis, which may have therapeutic potential in IDD.

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“…DLD is often associated with inflammatory status 9 and oxidative stresses. 10 AOS may be beneficial for preventing DLD progression. 11,12 Nanotechnology has provided the possibility of delivering drugs to target tissues via nanoparticles.…”

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confidence: 99%

Oligosaccharide nanomedicine of alginate sodium improves therapeutic results of posterior lumbar interbody fusion with cages for degenerative lumbar disease in osteoporosis patients by downregulating serum miR-155

Wang

Zhou

et al. 2017

IJN

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Degenerative lumbar disease (DLD) is a significant issue for public health. Posterior lumbar intervertebral fusion with cages (PLIFC) has high-level fusion rate and realignment on DLD. However, there are some complications following the surgery. Alginate oligosaccharides (AOS) have antioxidant and anti-inflammatory activities and may be suitable for infection therapy. MiR-155 is a biomarker associated with inflammatory and oxidative stress. AOS may promote PLIFC therapy by regulating miR-155. Pluronic nanoparticles and oligosaccharide nanomedicine of alginate sodium (ONAS) were prepared with ampicillin at size <200 nm. Ninety-six DLD osteoporosis patients received PLIFC and were evenly assigned into ONAS group (OG, oral administration of 100 mg ONAS daily) and control group (PG, 100 mg pluronic nanoparticles). Serum miR-155 level was measured by real-time quantitative PCR. The levels of superoxide dismutase (SOD), glutathione (GSH), aspartate aminotransaminase (AST), alanine aminotransferase (ALT), interleukin-1β (IL-1β), and interleukin-1 receptor antagonist (IL-1ra) were measured. Weighted mean difference (WMD), relative risk (RR), complications, surgery infection rate, fusion rate, and Japanese Orthopaedic Association (JOA) scores were used to evaluate therapeutic efficacy. After 1-month therapy, infection rates and side effects were lower in OG than those in PG (RR =0.64, 95% confidence interval [CI] [0.48, 0.84], P =0.001). The fusion rates were higher in OG than in PG (WMD =21.96, 95% CI [−0.24, 37.62], P =0.021). The JOA scores were higher in OG than in PG (RR =0.52, 95% CI [0.33, 0.84], P =0.007), and no significant difference was found for the visual analog scale and Oswestry Disability Index. Serum levels of miR-155, ALT, AST, and IL-1β were lower while SOD, GSH, and IL-1ra were higher in OG than in PG. MiR-155 mimic increased the levels of ALT, AST, and IL-1β and reduced the levels of SOD, GSH, and IL-1ra. In contrast, miR-155 inhibitor had reverse results. Therefore, ONAS has better improvement in complications and therapeutic effects on DLD by regulating serum miR-155.

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Autophagy Is a Protective Response to the Oxidative Damage to Endplate Chondrocytes in Intervertebral Disc: Implications for the Treatment of Degenerative Lumbar Disc

Cited by 37 publications

References 50 publications

β‑ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration

β‑ecdysterone protects against apoptosis by promoting autophagy in nucleus pulposus cells and ameliorates disc degeneration

Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

Oligosaccharide nanomedicine of alginate sodium improves therapeutic results of posterior lumbar interbody fusion with cages for degenerative lumbar disease in osteoporosis patients by downregulating serum miR-155

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