scholarly journals Regulation of catabolic gene expression in normal and degenerate human intervertebral disc cells: implications for the pathogenesis of intervertebral disc degeneration

2009 ◽  
Vol 11 (3) ◽  
pp. R65 ◽  
Author(s):  
S Jane Millward-Sadler ◽  
Patrick W Costello ◽  
Anthony J Freemont ◽  
Judith A Hoyland
Keyword(s):  
Gene Expression ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Catabolic Gene ◽  
Disc Cells

DNA Demethylation Regulates Anabolic and Catabolic Gene Expression in Intervertebral Disc Cells

2014 ◽  
Vol 4 (1_suppl) ◽  
pp. s-0034-1376587-s-0034-1376587
Author(s):  
N. Chutkan ◽  
R. Sangani ◽  
H. Zhou ◽  
S. Fulzele
Keyword(s):  
Gene Expression ◽  
Intervertebral Disc ◽  
Dna Demethylation ◽  
Catabolic Gene ◽  
Disc Cells

scholarly journals Overexpression of BNIP3 in Rat Intervertebral Disc Cells Can Trigger Autophagy-Related Apoptosis

2020 ◽  
Author(s):  
Ting-Sheng Wu ◽  
Shao-Yong Fan ◽  
Bin Zhang ◽  
Zhi-Qiang Tao ◽  
Hong Hua ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Low Back ◽  
Rt Pcr ◽  
Cell Staining ◽  
Apoptotic Protein ◽  
Disc Cells ◽  
Related Proteins ◽  
Western Blotting Assay

Abstract Background: Intervertebral disc degeneration (IDD) is the important cause of low back pain. Excessive apoptosis of intervertebral disc cells is the primary cause of IDD. BNIP3 is a member of Bcl-2 family and is widely involved in cell autophagy and apoptosis. However, the roles and mechanisms of BNIP3 in intervertebral disc cell autophagy and apoptosis are unclear.Results: In this study, the primary rat intervertebral disc cells were prepared and applied to study the effect of BNIP3 overexpression on their autophagy and apoptosis. RT-PCR and western blotting assay showed that BNIP3 overexpression significantly up-regulated the expression of autophagy and pro-apoptotic related proteins, including HIF-1α, Apaf-1, cleaved caspase 3, LC-3 and Beclin-1, while down-regulated the expression of anti-apoptotic protein Bcl-2. Subsequent cell staining detection of autophagy and apoptosis showed that BNIP3 overexpression significantly increased the autophagy and apoptosis of rat intervertebral disc cells. Furthermore, BNIP3 interference assay revealed that the effects of BNIP3 overexpression can be reversed by BNIP3 interference. Conclusions: The above findings suggested that BNIP3 enhanced autophagy of intervertebral disc cells and further triggered the apoptosis of intervertebral disc cells, eventually led to the development of intervertebral disc degeneration.

scholarly journals Integrated transcriptome and proteome analyses identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chen Xu ◽  
Shengchang Luo ◽  
Leixin Wei ◽  
Huiqiao Wu ◽  
Wei Gu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Regulatory Network ◽  
Intervertebral Disc Degeneration ◽  
Proteome Analysis ◽  
Label Free ◽  
Nucleus Pulposus Cells ◽  
Transcriptomic Data

Abstract Background Degeneration of intervertebral disc is a major cause of lower back pain and neck pain. Studies have tried to unveil the regulatory network using either transcriptomic or proteomic analysis. However, neither have fully elucidated the exact mechanism of degeneration process. Since post-transcriptional regulation may affect gene expression by modulating the translational process of mRNA to protein product, a combined transcriptomic and proteomic study may provide more insight into the key regulatory network of Intervertebral disc degeneration. Methods In order to obtain the proteomic and transcriptomic data, we performed label-free proteome analysis on freshly isolated nucleus pulposus cells and obtained transcriptome profiling data from the Gene Expression Omnibus repository. To identify the key regulatory network of intervertebral disc degeneration in nucleus pulposus cells, we performed bioinformatic analyses and established a protein-RNA interacting network. To validate the candidate genes, we performed in vitro experimentation and immunochemistry labeling to identify their potential function during nucleus pulposus degeneration. Results The label-free proteome analysis identified altogether 656 proteins, and 503 of which were differentially expressed between nucleus pulposus cells from degenerated or normal disc cells. Using the existing nucleus pulposus transcriptomic profiling data, we integrated the proteomic and transcriptomic data of nucleus pulposus cells, and established a protein-RNA interacting network to show the combined regulatory network of intervertebral disc degeneration. In the network, we found 9 genes showed significant changes, and 6 of which (CHI3L1, KRT19, COL6A2, DPT, TNFAIP6 and COL11A2) showed concordant changes in both protein and mRNA level. Further functional analysis showed these candidates can significantly affect the degeneration of the nucleus pulposus cell when altering their expression. Conclusions This study is the first to use combined analysis of proteomic and transcriptomic profiling data to identify novel regulatory network of nucleus pulposus cells in intervertebral disc degeneration. Our established protein-RNA interacting network demonstrated novel regulatory mechanisms and key genes that may play vital roles in the pathogenesis of intervertebral disc degeneration.

Gene Expression Changes in an Early Stage of Intervertebral Disc Degeneration Induced by Passive Cigarette Smoking

Spine ◽  
2006 ◽  
Vol 31 (5) ◽  
pp. 510-514 ◽  
Author(s):  
Hiroshi Uei ◽  
Hiromi Matsuzaki ◽  
Hiroshi Oda ◽  
Shinya Nakajima ◽  
Yasuaki Tokuhashi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cigarette Smoking ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Early Stage

scholarly journals AMPK as a Potential Therapeutic Target for Intervertebral Disc Degeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhen Wang ◽  
Jianxiong Shen ◽  
Erwei Feng ◽  
Yang Jiao
Keyword(s):  
Protein Kinase ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Therapeutic Target ◽  
Intervertebral Disc Degeneration ◽  
Cell Metabolism ◽  
Activation Process ◽  
Cellular Processes ◽  
Disc Cells ◽  
Remodeling Of Extracellular Matrix

As the principal reason for low back pain, intervertebral disc degeneration (IDD) affects the health of people around the world regardless of race or region. Degenerative discs display a series of characteristic pathological changes, including cell apoptosis, senescence, remodeling of extracellular matrix, oxidative stress and inflammatory local microenvironment. As a serine/threonine-protein kinase in eukaryocytes, AMP-activated protein kinase (AMPK) is involved in various cellular processes through the modulation of cell metabolism and energy balance. Recent studies have shown the abnormal activity of AMPK in degenerative disc cells. Besides, AMPK regulates multiple crucial biological behaviors in IDD. In this review, we summarize the pathophysiologic changes of IDD and activation process of AMPK. We also attempt to generalize the role of AMPK in the pathogenesis of IDD. Moreover, therapies targeting AMPK in alleviating IDD are analyzed, for better insight into the potential of AMPK as a therapeutic target.

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