Autophagy: A double-edged sword in intervertebral disk degeneration

Zhang, Shujun; Yang, Wei; Wang, Cheng; He, Wen-Si; Deng, Hong‐Wen; Yan, Yongping; Zhang, Jian; Xiang, Yong‐Xiao; Wang, Wenjun

doi:10.1016/j.cca.2016.03.016

Cited by 56 publications

(46 citation statements)

References 159 publications

(164 reference statements)

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“…Thus, we proved that IL-1β could induce apoptosis and autophagy in NP cells, but the relationships between them were still unclear. According to the available evidence, the role of autophagy on the survival of NP cells is a double-edged sword by adjusting to variational stress19. In this study, 3MA pretreatment dramatically further increased IL-1β-induced apoptosis, revealing that autophagy activation may protect against cell apoptosis as a compensatory mechanism.…”

Section: Discussionmentioning

confidence: 55%

IL-1β induces apoptosis and autophagy via mitochondria pathway in human degenerative nucleus pulposus cells

Shen

Zhou

et al. 2017

Sci Rep

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IL-1β has been reported highly expressed in degenerative intervertebral disc, and our previous study indicated IL-1β facilitates apoptosis of human degenerative nucleus pulposus (NP) cell. However, the underlying molecular mechanism remains unclear. We here demonstrate that IL-1β played a significantly pro-apoptotic effect under serum deprivation. IL-1β decreased Bcl-2/Bax ratio and enhanced cytochrome C released from mitochondria to cytosol, which proved mitochondria-meidated apoptosis was induced. Subsequently, mitochondria damage was detected under IL-1β stimualtion. In addition, IL-1β-mediated injuried mitochondria contributes to activate autophagy. However, pretreatment with the autophagy inhibitor 3-methyladenine showed the potential in further elevating the apoptosis rate induced by IL-1β in NP cells. Our results indicated that the mitochondrial pathway was involved in IL-1β-induced apoptosis of NP cells. Meanwhile, the damaged mitochondria-induced autophagy played a protective role against apoptosis, suggesting a postive feedback mechanism under inflammatory stress.

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Section: Discussionmentioning

confidence: 55%

IL-1β induces apoptosis and autophagy via mitochondria pathway in human degenerative nucleus pulposus cells

Shen

Zhou

et al. 2017

Sci Rep

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“…Many studies view autophagy as a double-edged sword in cell survival and there are contradictory reports on its impact in IDD [65,66]. Autophagy has been shown to have a positive effect on cell survival by mediating the selective removal of damaged cell components [54,67].…”

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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“…In contrast, genetic heredity is the predominant risk factor for degenerative disc disease and is estimated to cause over 70% of cases . Although the pathogenesis of IDD is not completely understood, it is well established that progressive loss of ECM, cell proliferation, inflammatory response, angiogenesis, apoptosis, autophagy, and oxidative stress play critical roles in the occurrence and development of disc degeneration …”

Section: Role Of Lncrnas In Iddmentioning

confidence: 99%

“…40,41 Although the pathogenesis of IDD is not completely understood, it is well established that progressive loss of ECM, cell proliferation, inflammatory response, angiogenesis, apoptosis, autophagy, and oxidative stress play critical roles in the occurrence and development of disc degeneration. [42][43][44][45][46][47] Like the well-known short non-coding RNAs such as miRNAs, 1 49 Overexpression of FAF1 is known to potentiate Fas-mediated apoptosis and suppress the degradation of ubiquitinated proteins, leading to a significant increase of cell death. 50,51 These authors also found that in addition to upregulation of the nearby enhancer-like lncRNA, RP11-296A18.3, FAF1 is significantly increased in degenerative discs compared with the normal discs.…”

Section: Ivdmentioning

confidence: 99%

lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis

et al. 2016

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The term long non-coding RNA (lncRNA) refers to a group of RNAs with length more than 200 nucleotides, limited protein-coding potential, and having widespread biological functions, including regulation of transcriptional patterns and protein activity, formation of endogenous small interfering RNAs (siRNAs) and natural microRNA (miRNA) sponges. Intervertebral disc degeneration (IDD) and osteoarthritis (OA) are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders. Numbers of lncRNAs are differentially expressed in human degenerative nucleus pulposus tissue and OA cartilage. Moreover, some lncRNAs have been shown to be involved in multiple pathological processes during OA, including extracellular matrix (ECM) degradation, inflammatory responses, apoptosis and angiogenesis. In this review, we summarize current knowledge concerning lncRNAs, from their biogenesis, classification and biological functions to molecular mechanisms and therapeutic potential in IDD and OA. are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders, leading to an enormous socioeconomic burden worldwide. IDD and OA are two major causes of disability and chronic pain, and their incidence has been increasing not only among older persons but also within younger adults in the past decades. It is estimated that approximately 80% adults will suffer chronic low back pain caused by IDD during their lifetime.1 Over 50% of patients with symptomatic OA are younger than 65 years old.

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Autophagy: A double-edged sword in intervertebral disk degeneration

Cited by 56 publications

References 159 publications

IL-1β induces apoptosis and autophagy via mitochondria pathway in human degenerative nucleus pulposus cells

IL-1β induces apoptosis and autophagy via mitochondria pathway in human degenerative nucleus pulposus cells

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

lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis

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