The effects of polymorphisms of death pathway genes and mitochondrial pathway genes in intervertebral disc degeneration

Eser, Betül; Eser, Olcay; Aslan, Esra; Dolgun, Habibullah

doi:10.5137/1019-5149.jtn.17927-16.0

Cited by 4 publications

(5 citation statements)

References 24 publications

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“…Apoptosis of NPCs leads to downregulation of ECM synthesis by activating the p53 signaling pathway (Jin et al, 2018). Apoptosis is also involved in several grades of IVD degeneration (Eser et al, 2017). Other factors, such as nutrients and aging, may also regulate the viability of, and ECM synthesis by NPCs (Barakat et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

miRNA-141 Induced Pyroptosis in Intervertebral Disk Degeneration by Targeting ROS Generation and Activating TXNIP/NLRP3 Signaling in Nucleus Pulpous Cells

Xing

et al. 2020

Front. Cell Dev. Biol.

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The role and mechanism of pyroptosis in intervertebral disk (IVD) degeneration are unclear. MicroRNAs (miRNAs) regulate the viability and function of nucleus pulposus cells (NPCs) in IVDs and are related to pyroptosis. We performed microarray analyses of normal and degenerated nucleus pulposus (NP) to assess the role of pyroptosis and identify key miRNAs in IVD degeneration. We also evaluated the underlying mechanism of miRNA-mediated pyroptosis in NPCs. In addition, we demonstrated the preventative effects of miRNAs on IVD degeneration in a rat model. The levels of the pyroptosis-related proteins cleaved caspase-1, N-terminal gasdermin D (GSDMD), interleukin (IL)-1β, and IL-18 in the degenerative NP were significantly higher than those in the normal NP. miRNA-141 was significantly upregulated in the degenerated NP. miR-141 mimic suppressed the matrix synthesis function of NPCs. By contrast, reactive oxygen species (ROS) generation, and the expression of TXNIP and NLRP3 were significantly downregulated by an miR-141 inhibitor. Furthermore, the miRNA-141 inhibitor prevented the degeneration of IVDs in vivo. Our findings suggest that miRNA-141 induces pyroptosis and extracellular matrix (ECM) catabolism in NPCs by increasing ROS generation and activating TXNIP/NLRP3 signaling. miRNA-141regulated pyroptosis may be a novel therapeutic target for IVD degeneration.

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Section: Introductionmentioning

confidence: 99%

miRNA-141 Induced Pyroptosis in Intervertebral Disk Degeneration by Targeting ROS Generation and Activating TXNIP/NLRP3 Signaling in Nucleus Pulpous Cells

Xing

et al. 2020

Front. Cell Dev. Biol.

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“…Simultaneously, autophagy caused by damaged mitochondria has a protective effect on cell apoptosis, suggesting a positive feedback mechanism under inflammatory stress conditions [93]. Eser et al [94] found a specific relationship between the Bcl-2 GG genotype and IDD, and the proportion of Bax-positive cells was associated with the IDD grade. Shang et al [95] also reported a relationship between the Bcl-2 gene polymorphism and IDD occurrence and severity.…”

Section: The Mitochondrial Pathway Induces Iddmentioning

confidence: 99%

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy

Zhang¹,

Hu²,

Peng³

et al. 2021

Int. J. Med. Sci.

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Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly induced by the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (ERS) pathway. This article mainly summarizes the factors that induce IDD and apoptosis, the relationship between the three apoptotic pathways and IDD, and potential therapeutic strategies. Preliminary animal and cell experiments show that targeting apoptotic pathway genes or drug inhibition can effectively inhibit IVD cell apoptosis and slow IDD progression. Targeted apoptotic pathway inhibition may be an effective strategy to alleviate IDD at the gene level. This manuscript provides new insights and ideas for IDD therapy.

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“…Bax, Bcl-2, capsase-3, and caspase-9 are some important parameters to evaluate cell apoptosis [7][8][9]. Previously, lots of studies have reported an increase in the expression of apoptotic genes (Bax and caspase-3/9) and a decrease in the expression of antiapoptotic gene (Bcl-2) in patients with disc degeneration [10,11].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol Suppresses Annulus Fibrosus Cell Apoptosis through Regulating Oxidative Stress Reaction in an Inflammatory Environment

Shan¹,

Zhang

et al. 2021

BioMed Research International

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During disc degeneration, the increase of inflammatory cytokines and decrease of disc cell density are two prominent features. Enhanced inflammatory reaction contributes to disc annulus fibrosus (AF) cell apoptosis. In this study, we investigated whether resveratrol can suppress AF cell apoptosis in an inflammatory environment. Rat disc AF cells were cultured in medium with or without tumor necrosis factor-α (TNF-α). Resveratrol was added along with the culture medium supplemented with TNF-α. Caspase-3 activity, cell apoptosis ratio, expression of apoptosis-associated molecules (Bcl-2, Bax, caspase-3, cleaved PARP, and cleaved caspase-3), reactive oxygen species (ROS) content, and the total superoxide dismutase (SOD) activity were measured. Our results showed that TNF-α significantly increased caspase-3 activity and AF cell apoptosis ratio and upregulated gene/protein expression of Bax, caspase-3, cleaved caspase-3, and cleaved PARP, whereas it downregulated the expression of Bcl-2. Moreover, TNF-α significantly increased ROS content but decreased the total SOD activity. Further analysis demonstrated that resveratrol partly attenuated the effects of TNF-α on AF cell apoptosis-associated parameters, decreased ROS content, and increased the total SOD activity in the AF cells treated with TNF-α. In conclusion, resveratrol attenuates inflammatory cytokine TNF-α-induced AF cell apoptosis through regulating oxidative stress reaction in vitro. This study sheds a new light on the protective role of resveratrol in alleviating disc degeneration.

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The effects of polymorphisms of death pathway genes and mitochondrial pathway genes in intervertebral disc degeneration

Abstract: GG genotype of Bcl-2 gene may influence the level of its expression and may be effective on the development of IVDD. Additionally, expression of Bax gene may be related with different grades of IVDD.

Cited by 4 publications

References 24 publications

miRNA-141 Induced Pyroptosis in Intervertebral Disk Degeneration by Targeting ROS Generation and Activating TXNIP/NLRP3 Signaling in Nucleus Pulpous Cells

miRNA-141 Induced Pyroptosis in Intervertebral Disk Degeneration by Targeting ROS Generation and Activating TXNIP/NLRP3 Signaling in Nucleus Pulpous Cells

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy

Resveratrol Suppresses Annulus Fibrosus Cell Apoptosis through Regulating Oxidative Stress Reaction in an Inflammatory Environment

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