Circular RNAs in nucleus pulposus cell function and intervertebral disc degeneration

Li, Zheng; Chen, Xin; Xu, Derong; Li, Shugang; Chan, Matthew T. V.; Wu, William Ka Kei

doi:10.1111/cpr.12704

Cited by 76 publications

(90 citation statements)

References 45 publications

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“…A large of studies shown that the degeneration mainly displays as a large number of the nucleus pulposus cell apoptosis and thus nucleus pulposus cells apoptosis plays a crucial role in IVDD [7,8]. TNF-α is a key proinflammatory cytokine and could induce the apoptosis of nucleus pulposus cells [9].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

et al. 2020

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Background: Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain, which is induced by multiple factors including increased apoptosis and decreased survival of nucleus pulposus cells. In this study, we evaluate the effect and potential mechanism of miR-660 on the nucleus pulposus cells apoptosis induced by TNF-α. Methods: First, we collected tissue of nucleus pulposus from IVDD and healthy controls. General characteristic of the IVDD and healthy control was also collected. And, we also collected nucleus pulposus cells that stimulated by TNF-α or control. miRNA microarray was performed to identify the differentially expressed miRNAs. Apoptosis rate and miR-660 relative expression was measured after stimulated with different concentration of TNF-α to identify the optimal concentration of TNF-α. Second, we successfully constructed antigomiR-660 to block the miR-660 expression in nucleus pulposus cells and then stimulated with TNF-α (100 ng/ml, 12 h). The apoptosis rates and relative protein expression were then measured again. The target association between miR-660 and SAA1 was confirmed by dual-luciferase reporter. Results: There was no significant difference between the age (IVDD: 39 ± 10 years, healthy controls: 36 ± 7 years), BMI and sex between IVDD and healthy controls. Microarray analysis found that miR-660 was significantly upregulated in IVDD and TNF-α treated groups, which was further identified by PCR. We found that the rate of apoptosis and miR-660 expression increased with TNF-α concentration increased. Finally, TNF-a with 100 ng/ml was used for further experiment. Compared with TNF-α group, TNF-α + antigomiR-660 could significantly downregulated the apoptosis rate and relative protein (c-Caspase3 and c-Caspase7). Dual-luciferase reporter revealed that miR-660 could directly binding to the SAA1 at 80-87 sites. Compared with TNF-α alone group, TNF-α + antigomiR-660 significantly up-regulated the SAA1 expression (P < 0.05). Conclusion: These results indicated that knockdown of miR-660 protected the nucleus pulposus from apoptosis that induced TNF-α via up-regulation of SAA1. Further studies should focus on the role of miR-660 in protecting IVDD in vivo.

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Section: Introductionmentioning

confidence: 99%

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

et al. 2020

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“…CircVMA21 obviously inhibited inflammatory cytokines-induced disk cells apoptosis and ECM degradation by functioning as competing endogenous RNAs to bind to miR-200c and, thus, regulate the targeting gene XIAP (Cheng et al, 2018). There were also several other identified circRNAs reported to participate in the pathogenesis of IDD in the past few years (Li et al, 2019). However, it remains undetermined how circRNAs play a part functionally in the involvement of mechanical loads during the IVD degeneration development.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating evidence have revealed that non-coding RNAs, including microRNAs (miRNAs) and circular RNAs (circRNAs), functionally participate in the pathophysiological process of IDD (Li et al, 2015(Li et al, , 2019. MiRNAs are highly conserved, short, and single stranded endogenous RNAs which can regulate the target mRNA expression via associating with AGO proteins (Bartel, 2004).…”

Section: Introductionmentioning

confidence: 99%

CircCOG8 Downregulation Contributes to the Compression-Induced Intervertebral Disk Degeneration by Targeting miR-182-5p and FOXO3

Xiang

Kang

Zhao

et al. 2020

Front. Cell Dev. Biol.

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Circular RNAs (circRNAs) have been increasingly demonstrated to play critical roles in the pathogenesis of various human diseases. Intervertebral disk degeneration (IDD) is recognized as the major contributor to lower back pain, and mechanical stress is a predominant trigger for IDD. However, little is known about the part that circRNAs play in the involvement of mechanical stress during IDD development. In the present study, we identified a novel circRNA and examined the role of this circRNA in a compression loading-induced IDD process. We detected the expression pattern of circCOG8 and observed its function in disk NP cells under mechanical stress. We conducted bioinformatics analysis, RNA immunoprecipitation experiment, and reporter gene assay to unveil the mechanism of the circCOG8 downregulation mediated IVD degeneration. Results showed that the circCOG8 expression was obviously downregulated by the mechanical stress in disk NP cells. CircCOG8 attenuated NP cells apoptosis, intracellular ROS accumulation, and ECM degradation in vitro and ex vivo. CircCOG8 directly interacted with miR-182-5p and, thus, modulated the FOXO3 expression to affect the compression-induced IDD progression. Altogether, the present study revealed that the circCOG8/miR-182-5p/FOXO3 pathway was an important underlying mechanism in the involvement of compression during the IDD progression. Intervention of circCOG8 is a new therapeutic strategy for IDD treatment.

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“…ECM degradation, abnormal apoptosis of NP cells, and in ammatory reaction are the main pathological processes of IDD. ECM proteins are mainly composed of collagen II and aggrecan, which are mainly secreted by NP cells [12]. Therefore, the balance between the growth and apoptosis of NP cells is key to the balance of the ECM and the development of IDD.…”

Section: Discussionmentioning

confidence: 99%

“…At present, it is thought that the pathogenesis of IDD is mainly related to aging, mechanical stress, degradation of the ECM marked by progressive loss of aggrecan and collagen II, and genetic factors [2]. Among them, ECM synthesis and degradation caused by the abnormal proliferation and apoptosis of NP cells are considered to be key factors in the pathogenesis of IDD [3,4].…”

Section: Introductionmentioning

confidence: 99%

Effects of microRNA-27a Targeting Smad1 on Intervertebral Disc Degeneration and Biological Characteristics of Nucleus Pulposus Cells

Tang

Zhang

et al. 2020

Preprint

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Objective: The present study aimed to analyze the expression of microRNA-27a (miR-27a) in intervertebral disc degeneration (IDD) and its effect on the biological characteristics of nucleus pulposus (NP) cells. Methods: An IDD rat model was established, and the expression of miR-27a and Smad1 in the intervertebral disc tissue was detected. An oxygen and glucose deprivation (OGD) NP cell model was established to simulate the IDD microenvironment, and the effects of downregulated miR-27a on the proliferation, apoptosis, inflammatory response, and extracellular matrix (ECM) proteins of OGD-NP cells were analyzed. The target relationship of miR-27a and Smad1 was verified by luciferase reporter assays, and siRNA-Smad1 was transfected to reverse the experiment. Results: The level of miR-27a in the IDD model group was significantly increased, whereas that of Smad1 was decreased compared with the sham group (P<0.05). Inhibition of miR-27a improved cell proliferation, and inhibited apoptosis, degradation of the ECM, and inflammatory response of OGD-NP cells compared with the OGD group (P<0.05). The results of the double luciferase reporter assays indicated that Smad1 was the target gene of miR-27a. Smad1 silencing reversed the increase in ECM proteins induced by inhibition of miR-27a; However, it did not affect cell proliferation and apoptosis. Conclusion: The expression levels of miR-27a were upregulated in IDD and it may be involved in the progression of IDD by promoting the apoptosis of NP cells and ECM degradation by targeting Smad1.

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Circular RNAs in nucleus pulposus cell function and intervertebral disc degeneration

Cited by 76 publications

References 45 publications

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1

CircCOG8 Downregulation Contributes to the Compression-Induced Intervertebral Disk Degeneration by Targeting miR-182-5p and FOXO3

Effects of microRNA-27a Targeting Smad1 on Intervertebral Disc Degeneration and Biological Characteristics of Nucleus Pulposus Cells

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