MicroRNA-494 promotes apoptosis and extracellular matrix degradation in degenerative human nucleus pulposus cells

Kang, Liang; Cao, Yang; Yu, Shun; Zhao, Kangcheng; Liu, Wei; Hua, Wenbin; Wang, Kun; Tu, Ji; Li, Shuai; Yin, Huipeng; Zhang, Yukun

doi:10.18632/oncotarget.15838

Cited by 38 publications

(30 citation statements)

References 48 publications

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“…A significant differential expression of some miRNAs between normal and degenerative NP tissues, and an association with the development and progression of IDD have been demonstrated, and many knockdown or overexpression experiments have been performed in vitro. For example, it has been demonstrated that MIR133a induces the downregulation of COL2A1 by targeting matrix metallopeptidase 9 (MMP9), causing the onset of IDD [ 34 ]; MIR146a suppresses IL-1β-induced MMP13, ADAM metallopeptidase with thrombospondin type 1 motif 4 (ADAMTS4), and ADAMTS5 expression in NP cells [ 35 ]; MIR98 or MIR27b downregulation contributes to the loss of COL2A1 in IDD [ 36 , 37 ]; MIR15a and MIR143 promote the progression of NP apoptosis by directly targeting BCL2 apoptosis regulator [ 38 , 39 ]; MIR15b silencing protects NP cells from IL-1β-induced ECM degradation by targeting SMAD3 [ 40 ]; MIR132 promotes ECM degradation [ 41 ] in human NP cells by direct targeting of growth differentiation factor 5 (GDF5, a member of TGFβ superfamily) which is also a target gene of MIR7 [ 37 ]; MIR210 promotes Fas-mediated apoptosis in human IDD by regulating the expression of homeobox A9 (HOXA9) [ 42 ]; MIR494 promotes ECM degradation and apoptosis of degenerative human NP cells by directly targeting SOX9 [ 43 ]; MIR10b is overexpressed in IDD and increased NP cell proliferation by targeting HOXD10 to derepress the RhoC-Akt signaling [ 44 ]; concerning miR-221, a recent paper investigated its role in the osteogenic differentiation of degenerated annulus fibrosus cells [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells

Penolazzi

Lambertini

Bergamin

et al. 2018

Aging

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The aim of this study was to investigate the role of an antichondrogenic factor, MIR221 (miR-221), in intervertebral disc degeneration (IDD), and provide basic information for the development of a therapeutic strategy for the disc repair based on specific nucleic acid based drugs, such as miR-221 silencing. We established a relatively quick protocol to minimize artifacts from extended in vitro culture, without selecting the different types of cells from intervertebral disc (IVD) or completely disrupting extracellular matrix (ECM), but by using the whole cell population with a part of resident ECM. During the de-differentiation process miR-221 expression significantly increased. We demonstrated the effectiveness of miR-221 silencing in driving the cells towards chondrogenic lineage. AntagomiR-221 treated cells showed in fact a significant increase of expression of typical chondrogenic markers including COL2A1, ACAN and SOX9, whose loss is associated with IDD. Moreover, antagomiR-221 treatment restored FOXO3 expression and increased TRPS1 expression levels attenuating the severity grade of degeneration, and demonstrating in a context of tissue degeneration and inflammation not investigated before, that FOXO3 is target of miR-221. Data of present study are promising in the definition of new molecules useful as potential intradiscal injectable biological agents.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells

Penolazzi

Lambertini

Bergamin

et al. 2018

Aging

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“…39 Extreme apoptosis has been found to reduce the activity of the nucleus pulposus and decrease extracellular matrix changes in synthesis and composition, which further contributes to IDD pathology. 40 The histological grades evaluated at week 4 and week 8 in three groups. Samples from 48 rats (sixteen in each group) were used for imageological and histopathologic analysis.…”

Section: Spermidine Ameliorates Rats Intervertebral Disc Degeneratimentioning

confidence: 99%

Spermidine promotes nucleus pulposus autophagy as a protective mechanism against apoptosis and ameliorates disc degeneration

Zheng

Wang

Chen

et al. 2018

J Cellular Molecular Medi

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Spermidine has therapeutic effects in many diseases including as heart diastolic function, myopathic defects and neurodegenerative disorders via autophagy activation. Autophagy has been found to mitigate cell apoptosis in intervertebral disc degeneration (IDD). Accordingly, we theorize that spermidine may have beneficial effects on IDD via autophagy stimulation. In this study, spermidine's effect on IDD was evaluated in tert‐butyl hydroperoxide (TBHP)‐treated nucleus pulposus cells of SD rats in vitro as well as in a puncture‐induced rat IDD model. We found that autophagy was actuated by spermidine in nucleus pulposus cells. In addition, spermidine treatment weakened the apoptotic effects of TBHP in nucleus pulposus cells. Spermidine increased the expression of anabolic proteins including Collagen‐II and aggrecan and decreased the expression of catabolic proteins including MMP13 and Adamts‐5. Additionally, autophagy blockade using 3‐MA reversed the beneficial impact of spermidine against nucleus pulposus cell apoptosis. Autophagy was thus important for spermidine's therapeutic effect on IDD. Spermidine‐treated rats had an accentuated T2‐weighted signal and a diminished histological degenerative grade than vehicle‐treated rats, showing that spermidine inhibited intervertebral disc degeneration in vivo. Thus, spermidine protects nucleus pulposus cells against apoptosis through autophagy activation and improves disc, which may be beneficial for the treatment of IDD.

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“…MiR-21 promotes human NPCs proliferation by affecting PTEN/AKT signaling [10]. MiR-494 induced cell apoptosis via directly combining with SOX9 in human degenerative NPCs [11]. Therefore, miRNAs might play an important role in the development and progression of IDD through regulating NPCs proliferation and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative disc cells following hyperbaric oxygen treatment

Lin

Niu

Yuan

et al. 2020

Preprint

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Background: MicroRNA (miRNA) plays a vital role in the intervertebral disc (IVD) degeneration. The expression level of miR-573 was downregulated whereas Bax was upregulated notably in human degenerative nucleus pulposus cells (NPCs). In this study, we aimed to investigate the role of miR-573 in human degenerative NPCs following hyperbaric oxygen (HBO) treatment. Methods: NPCs were separated from human degenerated IVD tissues. The control cells were maintained in 5% CO2/95% air and the hyperoxic cells were exposed to 100% O2 at 2.5 atmospheres absolute. MiRNA expression profiling was performed via microarray and confirmed by real-time PCR, and miRNA target genes were identified using bioinformatics and luciferase reporter assays. The mRNA and protein levels of Bax were measured. The proliferation of NPCs were detected using MTT assay. The protein expression levels of Bax, cleaved caspase 9, cleaved caspase 3, pro-caspase 9 and pro-caspase 3 were examined.Results: Bioinformatics analysis indicated that the 3′ untranslated region (UTR) of the Bax mRNA contained the “seed-matched-sequence” for hsa-miR-573, which was validated via reporter assays. MiR-573 was induced by HBO and simultaneous suppression of Bax was observed in NPCs. Knockdown of miR-573 resulted in upregulation of Bax expression in HBO-treated cells. In addition, overexpression of miR-573 by HBO increased cell proliferation and coupled with inhibition of cell apoptosis. The cleavage of pro‑caspase 9 and pro‑caspase 3 was suppressed while the levels of cleaved caspase 9 and caspase 3 were decreased in HBO-treated cells. Transfection with anti-miR-573 partly suppressed the effects of HBO. Conclusion: Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative NPCs following HBO treatment.

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MicroRNA-494 promotes apoptosis and extracellular matrix degradation in degenerative human nucleus pulposus cells

Cited by 38 publications

References 48 publications

MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells

MicroRNA-221 silencing attenuates the degenerated phenotype of intervertebral disc cells

Spermidine promotes nucleus pulposus autophagy as a protective mechanism against apoptosis and ameliorates disc degeneration

Mir-573 regulates cell proliferation and apoptosis by targeting Bax in human degenerative disc cells following hyperbaric oxygen treatment

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