MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells

Lv, Feng; Huang, Yingzi; Lv, Wentao; Yang, Longbiao; Li, Feng; Fan, Jingli; Sun, Juan

doi:10.12659/msm.898660

Cited by 46 publications

(30 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study suggested that overexpression of miR-146a significantly decreased the levels of pro-inflammatory cytokines, including IL-1b, TNF-α, and IL-6 by targeting the TARF6/NFκB pathway. It is indicated that miR-146a ameliorates inflammation via the TRAF6/NF-kB pathway in intervertebral disc cells 26,27 . Our results lend credence to the previous study suggesting that HCG18, acting as a miR-146a-5p sponge, accelerate IDD progression via the miR-146a-5p/TARF6/NFκB axis.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression

Jiang

Wang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Intervertebral disc degeneration (IDD) is associated with the deterioration of nucleus pulposus (NP) cells due to hypertrophic differentiation and calcification. Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in the development of IDD. Using bioinformatics prediction, we hereby sought to identify the lncRNAs that regulate the expression of microRNA-146a-5p (miR-146a-5p), an IDD-related inflammatory factor. Our study demonstrated that lncRNA HCG18 acted as an endogenous sponge to down-regulate miR-146a-5p expression in the NP cells by directly binding to miR-146a-5p. In addition, HCG18 expression was up-regulated in the patients with IDD, bulging or herniated discs, and its level was positively correlated with the disc degeneration grade. In vitro, miR-146a-5p up-regulation HCG18 retarded the growth of NP cells by decreasing S phase of cell cycle, inducing cell apoptosis, recruitment of macrophages and hypercalcification. Conversely, down-regulation of miR-146a-5p exerted opposite effects. Furthermore, we elucidated that TRAF6, a target gene by miR-146a-5p, was modulated by HCG18 expression. Restore of TRAF6 expression by virus infection reserved the effect of HCG18 on the NP cells. Altogether, our data indicated that HCG18 suppressed the growth of NP cells and promoted the IDD development via the miR-146a-5p/TRAF6/NFκB axis.

show abstract

Section: Discussionmentioning

confidence: 99%

Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression

Jiang

Wang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…NF‐κB signaling activates transcription factors in response to inflammation, cellular damage, and tissue degeneration . Many reports have shown that the NF‐κB signaling pathway has an important role in IDD . Therefore, we investigated whether the RADA‐KPSS peptide could protect TNF‐α‐treated NPCs by inhibiting NF‐κB signaling.…”

Section: Discussionmentioning

confidence: 99%

“…6,40 Many reports have shown that the NF-jB signaling pathway has an important role in IDD. 41,42 Therefore, we investigated whether the RADA-KPSS peptide could protect TNF-a-treated NPCs by inhibiting NF-jB signaling. Initially, the immunofluorescence of NF-jB-p65 was detected mainly in the cytoplasm of NPCs in the presence of RADA16-I, whereas the nuclear location of p65 protein was observed in TNF-a-treated NPCs cultured with both RADA16-I and RADA-KPSS peptides.…”

Section: Discussionmentioning

confidence: 99%

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

Cheng

et al. 2017

J Biomedical Materials Res

View full text Add to dashboard Cite

Although nucleus pulposus (NP) tissue engineering has achieved tremendous success, researches still face the huge obstacles in maintaining cell survival and function. A novel functional self-assembled peptide RADA-KPSS was constructed by conjugating BMP-7 short active fragment (KPSS) to the C-terminus of RADA16-I that displays anti-inflammatory and anti-apoptosis effects. However, whether this functional self-assembled RADA-KPSS peptide can alleviate inflammation and NPC apoptosis induced by tumor necrosis factor-alpha (TNF-α) has not been studied. Therefore, we cultured NPCs treated with TNF-α for 48 h with the RADA-KPSS peptide, and compared the results to those with RADA16-I peptide. The cell apoptosis rate, inflammatory mediator secretion, expression of matrix-degrading enzymes, and extracellular matrix (ECM) protein levels were evaluated. The expression of nuclear factor-κB-p65 (NF-κB-p65) protein was also tested. TNF-α-treated NPCs cultured with the RADA16-I peptide showed up-regulated gene expression for matrix-degrading enzymes, such as matrix metalloproteinases-3 (MMP-3), MMP-9, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-4), and down-regulated gene expression for ECM proteins such as aggrecan, collagen II, and Sox-9. The RADA-KPSS peptide could attenuate the expression of MMP-3, MMP-9, and ADAMTS-4, promote accumulation of ECM proteins, and increase secretion of glycosaminoglycan as compared with the RADA16-I peptide. Moreover, the TNF-α-damaged NPCs was further demonstrated to inhibit NF-κB-p65, IL-1, IL-6, and prostaglandin E-2 proteins and decrease cell apoptosis in RADA-KPSS peptide. In conclusion, the functional self-assembled RADA-KPSS peptides have anti-inflammatory and anti-apoptotic effects by promoting anabolic processes and inhibiting catabolic processes in intervertebral disk degeneration. These peptides may be feasible for clinical applications in NP tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1082-1091, 2018.

show abstract

“…For example, Hu et al reported that miR-194 and miR-515 can relieve the biosynthesis of chondroitin sulfate during human IDD development (19). Lv et al suggest that miR-146a over-expression can promote IDD through regulating TRAF/NF-κB pathway (20). miR-15 has been found upregulated in IDD and it can promote IDD by targeting MAP3K9 (21).…”

Section: Discussionmentioning

confidence: 99%

Role of miR‑589‑3p in human lumbar disc degeneration and its potential mechanism

Wang

2017

Exp Ther Med

View full text Add to dashboard Cite

Abstract. The present study aimed to investigate the role of miR-589-3p in lumbar disc degeneration (LDD) and to explore the underlying mechanisms. Nucleus pulposus (NP) cells were stimulated with lipopolysaccharide (LPS) to simulate an in vitro model of intervertebral disc degeneration. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of microRNA (miR)-589-3p in the NP cells, and the results demonstrated that the increased expression of miR-589-3p in LPS stimulated NP cells compared with the control. To further investigate the role of miR-589-3p in LDD, a human NP cell line with high/low miR-589-3p expression was generated using miR-589-3p mimics/inhibitors. In addition, a human NP cell inflammation model was conducted by LPS (10 µM) treatment. Western blot analysis and RT-qPCR were performed for detection of associated genes and proteins. Protein levels of pro-inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 were evaluated by ELISA. Flow cytometry was used for cell apoptosis determination. Furthermore, Targetscan was used to predict potential targets of miR-589-3p, and a dual luciferase reporter assay was used to verify the prediction. The findings verified that miR-589-3p was significantly upregulated in LDD. In vitro, miR-589-3p mimics/inhibitors significantly increased/reduced the production of TNF-α, IL-1β and IL-6 in LPS stimulated NP cells. Furthermore, miR-589-3p mimics/inhibitors significantly promoted/inhibited LPS stimulated NP cell apoptosis. MiR-589-3p mimics/inhibitors significantly repressed/enhanced type II collagen and aggrecan expression in LPS stimulated NP cells. In addition, it was demonstrated that mothers against decapentaplegic homolog (Smad) 4 was a direct target gene of miR-589-3p, and was negatively regulated by miR-589-3p in NP cells. In conclusion, miR-589-3p may function as a promoter in LDD development via the regulation of Smad4.

show abstract

MicroRNA-146a Ameliorates Inflammation via TRAF6/NF-κB Pathway in Intervertebral Disc Cells

Cited by 46 publications

References 26 publications

Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression

Long non-coding HCG18 promotes intervertebral disc degeneration by sponging miR-146a-5p and regulating TRAF6 expression

Functional self‐assembled peptide scaffold inhibits tumor necrosis factor‐alpha‐induced inflammation and apoptosis in nucleus pulposus cells by suppressing nuclear factor‐κB signaling

Role of miR‑589‑3p in human lumbar disc degeneration and its potential mechanism

Contact Info

Product

Resources

About