scholarly journals Circ_0004354 might compete with circ_0040039 to induce NPCs death and inflammatory response by targeting miR-345-3p-FAF1/TP73 axis in intervertebral disc degeneration

2022 ◽  
Vol 2022 ◽  
pp. 1-21
Author(s):  
Yongjin Li ◽  
Xiaojing Wu ◽  
Jianhua Li ◽  
Lilong Du ◽  
Xuke Wang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Pathological Process ◽  
Circular Rnas ◽  
Nucleus Pulposus Cells ◽  
Promising Therapeutic Target ◽  
Pathological Mechanism ◽  
Ecm Degradation

The abnormal function of nucleus pulposus cells (NPCs) plays a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Recent studies have demonstrated that circular RNAs (circRNAs) are involved in the pathological process of IVDD by regulating NPCs’ function. Nevertheless, the investigation on circRNA-circRNA interaction has not yet been reported. Here, we identified the top upregulated circ_0040039 and circ_0004354 in IVDD, derived from the syntrophin beta 2 gene but had different degrees of biological functions. Accumulating studies have reported PANoptosis is composed of apoptosis, pyroptosis, and necroptosis. Based on this, we think there should be a new pro-inflammatory cell death PAoptosis in the form of apoptosis and pyroptosis. Circ_0004354 might compete with circ_0040039 to induce the development of IVDD by modulating miR-345-3p-FAF1/TP73 axis-mediated PAoptosis, inflammatory response, growth inhibition, and ECM degradation of NPCs. Thus, these findings offer a novel insight into the circRNAs-mediated posttranscriptional regulatory network in IVDD, contributing to further clarification of the pathological mechanism of IVDD to develop a promising therapeutic target for IVDD diseases.

A novel mechanism of intervertebral disc degeneration: imbalance between autophagy and apoptosis

Epigenomics ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 1095-1108
Author(s):  
Guoyong Xu ◽  
Chong Liu ◽  
Jie Jiang ◽  
Tuo Liang ◽  
Chaojie Yu ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Expression Profiles ◽  
Circular Rna ◽  
Molecular Structures ◽  
Circular Rnas ◽  
Nucleus Pulposus Cells ◽  
Competitive Endogenous Rna

Aim: To identify a key competitive endogenous RNA network for intervertebral disc degeneration. Materials & methods: Based on circular RNA, microRNA and mRNA expression profiles of nucleus pulposus cells, a variety of bioinformatics methods were used to screen key molecular structures and construct competitive endogenous RNA networks. Results: 190 upregulated genes and 77 downregulated genes were identified. Gene ontology/Kyoto Encyclopedia of Genes and Genomes functional analysis showed that autophagy was out of balance with apoptosis. Nine hub genes, five hub microRNAs and eight hub circular RNAs were obtained through progressive reverse prediction and verification. Conclusion: We believe that disc degeneration is caused by an imbalance between autophagy and apoptosis in nucleus pulposus cells, which may provide nonsurgical treatment for the future delay or prevention of spinal degenerative diseases associated with intervertebral disc degeneration.

scholarly journals Dysregulated MiR-3150a-3p Promotes Lumbar Intervertebral Disc Degeneration by Targeting Aggrecan

2018 ◽  
Vol 45 (6) ◽  
pp. 2506-2515 ◽  
Author(s):  
Bin Zhang ◽  
Wei Guo ◽  
Chao Sun ◽  
Hui-Quan Duan ◽  
Bing-Bing Yu ◽  
...  
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Musculoskeletal Diseases ◽  
Circular Rnas ◽  
Low Back ◽  
Nucleus Pulposus Cells ◽  
Lumbar Intervertebral Disc

Background/Aims: Low back pain has become one of the most common musculoskeletal diseases in the world. Studies have shown that intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the mechanisms underlying IDD remain largely unknown. Research over the past decade has suggested critical roles for microRNAs (miRNAs) in natural growth and disease progression. However, it remains poorly understood whether circular RNAs participate in IDD. Methods: Clinical IDD samples were collected from 20 patients who underwent discectomy. Weighted gene co-expression network analysis was used to identify the co-expression miRNA network modules (highly co-expressed clusters of miRNAs) that were associated with IDD grade. Results: miR-3150a-3p was the most significantly up-regulated miRNA in module “Blue.” Notably, aggrecan (ACAN) was identified as a direct target gene of miR-3150a-3p and ACAN expression was regulated by miR-3150a-3p. Overexpression of miR-3150a-3p decreased ACAN expression in nucleus pulposus cells, whereas inhibition of miR-3150a-3p increased ACAN expression. In addition, ACAN expression was negatively correlated with IDD grade. Conclusion: Our study suggests that the reduction of ACAN expression induced by the upregulation of miR-3150a-3p might participate in the development of IDD.

scholarly journals The long non-coding RNA NEAT1 contributes to extracellular matrix degradation in degenerative human nucleus pulposus cells

2018 ◽  
Vol 243 (7) ◽  
pp. 595-600 ◽  
Author(s):  
Zhi Ruan ◽  
Hui Ma ◽  
Jing Li ◽  
Huiyong Liu ◽  
Haoruo Jia ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Mapk Signaling ◽  
Rt Pcr ◽  
Nucleus Pulposus Cells ◽  
Erk Mapk ◽  
Ecm Degradation ◽  
Lncrna Neat1

Intervertebral disc degeneration is a complex disease involving genetic and environmental factors and multiple cellular processes. The role and expression of the lncRNA NEAT1 were assessed in intervertebral disc degeneration. NEAT1 expression was assessed in degenerative and control nucleus pulposus using RT-PCR. Western blotting and RT-PCR were also used to investigate p53 and p21 levels in nucleus pulposus tissues. NEAT1 function in degenerative nucleus pulposus cells was assessed with gain- and loss-of-function experiments. ERK/MAPK signaling was also examined. NEAT1, p53, and p21 were dramatically upregulated in intervertebral disc degeneration. Furthermore, catabolic MMP13 and ADAMTS5 were dysregulated and collagen II and aggrecan were downregulated after NEAT1 overexpression. This effect was reversed by transfection with si-NEAT1 in degenerative nucleus pulposus cells. In addition, NEAT1 was found to affect the activation of the ERK/MAPK pathway. The NEAT1-induced ECM degradation may involve ERK1/2/MAPK signaling. LncRNA NEAT1 may represent a novel molecular target for intervertebral disc degeneration treatment by preventing nucleus pulposus ECM degradation. Impact statement For the first time, our study demonstrates that lncRNA NEAT1 plays a role in the occurrence and development of IDD by participating in extracellular matrix remodeling. This lncRNA regulates catabolic MMP13 and ADAMTS5 and anabolic collagen II and aggrecan by affecting the ERK/MAPK signaling pathway in degenerative human nucleus pulposus (NP) cells. Our research provides a scientific basis for targeting of NEAT1 for the IDD.

scholarly journals Arginase II Promotes Intervertebral Disc Degeneration Through Exacerbating Senescence and Apoptosis Caused by Oxidative Stress and Inflammation via the NF-κB Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Fudong Li ◽  
Xiaofei Sun ◽  
Bing Zheng ◽  
Kaiqiang Sun ◽  
Jian Zhu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Therapeutic Strategy ◽  
Opposite Effect ◽  
Nucleus Pulposus Cells ◽  
Cellular Processes ◽  
Arginase Ii

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which imposes massive clinical and socioeconomic burdens. Previous studies have demonstrated that oxidative stress and inflammation-induced senescence and apoptosis of nucleus pulposus cells (NPCs) are the main cellular processes that cause IDD. Arginase II (ARG2), an enzyme involved in a variety of pathological processes, including cellular senescence, apoptosis, oxidative stress, and inflammation, has been shown to promote degeneration in several degenerative diseases, including osteoarticular diseases. Based on previous studies, we hypothesized that ARG2 deficiency might be conducive to the treatment of IDD by inhibiting the dyshomeostasis of the extracellular matrix (ECM), and the oxidative stress and inflammatory response-induced senescence and apoptosis via NF-κB. In this study, we found that ARG2 deficiency inhibited senescence and apoptosis of NPCs, and degeneration of the ECM induced by oxidative stress and the inflammatory response. Similar results were found with the selective NF-κB pathway inhibitor JSH-23. In contrast, overexpression of ARG2 had the opposite effect. Taken together, our results suggest that ARG2 deficiency prevents IDD via NF-κB, and may therefore, be a potential therapeutic strategy for IDD.

scholarly journals Ligustrazine Prevents Intervertebral Disc Degeneration via Suppression of Aberrant TGFβ Activation in Nucleus Pulposus Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Shufen Liu ◽  
Yuhao Cheng ◽  
Yuqi Tan ◽  
Jingcheng Dong ◽  
Qin Bian
Keyword(s):  
Growth Factor ◽  
Mouse Model ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Ex Vivo ◽  
Tissue Growth ◽  
Nucleus Pulposus Cells

Objectives. Aberrant transforming growth factor β (TGFβ) activation is detrimental to both nucleus pulposus (NP) cells and cartilage endplates (CEPs), which can lead to intervertebral disc degeneration (IDD). Ligustrazine (LIG) reduces the expression of inflammatory factors and TGFβ1 in hypertrophic CEP to prevent IDD. In this study, we investigate the effects of LIG on NP cells and the TGFβ signaling. Design. LIG was injected to the lumbar spinal instability (LSI) mouse model. The effect of LIG was evaluated by intervertebral disc (IVD) score in the LSI mouse model. The expression of activated TGFβ was examined using immunostaining with pSmad2/3 antibody. The upright posture (UP) rat model was also treated and evaluated in the same manner to assess the effect of LIG. In ex vivo study, IVDs from four-week old mice were isolated and treated with 10−5, 10−6, and 10−7 M of LIG. We used western blot to detect activated TGFβ expression. TGFβ-treated human nucleus pulposus cells (HNPCs) were cotreated with optimized dose of LIG in vitro. Immunofluorescence staining was performed to determine pSmad2/3, connective tissue growth factor (CCN2), and aggrecan (ACAN) expression levels. Results. IVD score and the percentage of pSmad2/3+ NP cells were low in LIG-treated LSI mice in comparison with LSI mice, but close to the levels in the Sham group. Similarly, LIG reduced the overexpression of TGFβ1 in NP cells. The inhibitory effect of LIG was dose dependent. A dose of 10−5 M LIG not only strongly attenuated Smad2/3 phosphorylation in TGFβ-treated IVD ex vivo but also suppressed pSmad2/3, CCN2, and ACAN expression in TGFβ-treated NP cells in vitro. Conclusions. LIG prevents IDD via suppression of TGFβ overactivation in NP cells.

Sign in / Sign up

Export Citation Format

Share Document