Resveratrol attenuates high glucose-induced nucleus pulposus cell apoptosis and senescence through activating the ROS-mediated PI3K/Akt pathway

Wang, Wenping; Li, Pei; Xu, Jiagang; Wu, Xiangkun; Guo, Zhaobing; Fan, Lijing; Song, Ran; Wang, Jianli; Li, Wei; Teng, Haijun

doi:10.1042/bsr20171454

Cited by 64 publications

(77 citation statements)

References 38 publications

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“…There are two types of DM (type 1 DM and type 2 DM) with approximately 90% of DM patients are type 2 DM [1]. Accumulating evidence has shown that DM is a crucial effecter in the progression of intervertebral disc degeneration [2][3][4][5][6]. The morbidity of disc degeneration is much higher in DM patients than that in non-DM patients [7].…”

Section: Introductionmentioning

confidence: 99%

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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Diabetes mellitus (DM) is an important risk factor of intervertebral disc degeneration. A high glucose niche-mediated disc cell apoptosis is an implicate causative factor for the spine degenerative diseases related with DM. However, the effects of a high glucose niche on disc annulus fibrosus (AF) cell apoptosis and the potential signaling transduction pathway is unclear. The present study is to investigate the effects of high glucose on disc AF cell apoptosis and the role of two potential signaling pathways in this process. Rat AF cells were cultured in baseline medium or medium with different concentrations (0.1 and 0.2 M) of glucose for 3 days. Flow cytometry was used to assess the degree of apoptosis. Activity of caspase 3/9 was evaluated by chemical kit. Expression of pro-apoptotic and anti-apoptotic molecules was analyzed by real-time polymerase chain reaction and Western blot. In addition, activity of the C-Jun NH2-terminal kinases (JNK) pathway and p38 mitogen-activated protein kinase (MAPK) pathway was evaluated by Western blot. Compared with the control group, high glucose culture increased cell apoptosis ratio and caspase-3/9 activity, up-regulated expression of bax, caspase-3, cleaved caspase-3 and cleaved PARP, and down-regulated expression of bcl-2 in a glucose concentration-dependent manner. Additionally, high glucose culture increased expression of the p-JNK and p-p38 MAPK in a concentration-dependent manner. Further results showed that inhibition of the JNK or p38 MAPK pathway attenuated the effects of high glucose on AF cell apoptosis. Together, high glucose promoted disc AF cell apoptosis through regulating the JNK pathway and p38 MAPK pathway in a glucose concentration-dependent manner.

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Section: Introductionmentioning

confidence: 99%

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

et al. 2019

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“…Moreover, High glucose treated MSC exhibited significantly decreased cell migration, increased cell senescence and higher intracellular reactive oxygen species . However, reduction in glucose concentration could led to decreased cell apoptosis and increased proliferation rate of MSC …”

Section: Introductionmentioning

confidence: 95%

The effect of high glucose on the biological characteristics of nucleus pulposus‐derived mesenchymal stem cells

Liu

et al. 2020

Cell Biochemistry & Function

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Diabetes mellitus (DM) is a dependent risk factor in the progression of intervertebral disc degeneration (IVDD). High glucose supply has negative effects on nucleus pulpous (NP) cell and mesenchymal stem cell (MSC) biology. However, the effect of hyperglycaemia on the biological characterization of nucleus pulpous-derived mesenchymal stem cell (NPMSC) has not been investigated previously. Therefore, further exploration of the effects of DM-associated hyperglycaemia on NPMSC biology is important to better understand and develop endogenous repair strategies of DM patient-associated IVDD. Therefore, the cell biological characteristics were compared between NPMSC cultured in media with low glucose concentration (LG-NPMSC) and high glucose concentration (HG-NPMSC). The results demonstrated that HG-NPMSC showed significantly decreased cell proliferation, colony formation ability, migration and wound-healing capability compared with those of LG-NPMSC. HG-NPMSC also showed significantly decreased expressions of stemness genes and mRNA and protein expressions of silent information regulator protein 1 (SIRT1), SIRT6, hypoxia inducible factor-1α (HIF-1α) and glucose transporter 1 (GLUT-1), whereas increased cell apoptosis, cell senescence and caspase-3 expression. These results suggest that high glucose may decrease proliferation and stemness maintenance ability and increase apoptosis and senescence of NPMSC.Significance of the study: We found that high glucose concentration significantly decreased cell proliferation, colony formation ability, migration and wound-healing capability of nucleus pulposus-derived mesenchymal stem cells. Moreover, high glucose cultured nucleus pulposus-derived mesenchymal stem cells showed significantly decreased expression of stemness genes, related mRNA and protein, whereas increased cell apoptosis, cell senescence and expression of caspase-3. The present study indicated that better control of high concentration glucose in the early stage of diabetes mellitus should be recommended to prevent or limit intervertebral disc degeneration. K E Y W O R D S-high glucose, nucleus pulposus-derived mesenchymal stem cells, proliferation, apoptosis, senescence

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“…For example, sirt6 has shown potent anti-senescent and anti-apoptotic properties in models of age-related degenerative disease (6). Furthermore, overproduction of reactive oxygen species (ROS) has been reported to be involved in the senescence and apoptosis of NP cells and may accelerate the degenerative process (7). Previous studies also demonstrated that tumor necrosis factor-α promotes changes in the production of extracellular matrix (EcM) molecules, tissue degradation (8) and premature senescence of NP cells (9,10).…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

2020

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The aim of the present study was to investigate the role of the long non-coding (lnc)RNA PART1 in nucleus pulposus (NP) cells derived from patients with intervertebral disc degeneration (Idd). The level of PART1 in degenerative NP tissues from patients with Idd, bulging and herniated discs was measured by reverse transcription-quantitative PcR (RT-qPcR) analysis. NP cells were isolated from patients with Idd and transfected with siPART1, after which time the growth ability of the NP cells was evaluated by cell counting Kit-8 and colony formation assays, and cell apoptosis was measured by flow cytometry. The levels of the cell proliferation marker Ki-67 and the apoptosis marker cleaved caspase-3, and the levels of genes related to extracellular matrix (EcM) synthesis and degradation, were also evaluated by western blotting and RT-qPcR, as appropriate. Bioinformatics methods predicted that miR-93 was sponged by PART1, and matrix metallopeptidase (MMP)2 was targeted by miR-93, which was further confirmed by dual-luciferase reporter assay. The levels of miR-93 and MMP2 were also measured in NP tissues, and further rescue experiments were performed to confirm the role of the PART1/miR-93/MMP2 pathway in NP cells. PART1 was found to be upregulated in degenerative NP tissues, and siPART1 caused an increase in cell growth ability and EcM synthesis, whereas it decreased cell apoptosis and EcM degradation in NP cells. miR-93 was downregulated and MMP2 was upregulated in degenerative NP tissues. Rescue experiments indicated that the effects of miR-93 inhibitor on NP cells were abolished by siPART1, and the effect of miR-93 mimic on NP cells was rescued by MMP2 overexpression. Thus, the results of the present study demonstrated that PART1 may regulate NP cell degeneration through the miR-93/MMP2 pathway. These findings indicate a novel signaling axis in NP cells that may be explored for the treatment of Idd.

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Resveratrol attenuates high glucose-induced nucleus pulposus cell apoptosis and senescence through activating the ROS-mediated PI3K/Akt pathway

Cited by 64 publications

References 38 publications

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

High glucose promotes annulus fibrosus cell apoptosis through activating the JNK and p38 MAPK pathways

The effect of high glucose on the biological characteristics of nucleus pulposus‐derived mesenchymal stem cells

Long non-coding RNA PART1 promotes intervertebral disc degeneration through regulating the�miR‑93/MMP2 pathway in nucleus pulposus cells

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