Programmed cell death in intervertebral disc degeneration

The intervertebral disc degeneration (IDD) with increasing aging mainly manifests as low back pain (LBP) accompanied with a loss of physical ability. These pathological processes can be preliminarily interpreted as a series of changes at cellular level. In addition to cell death, disc cells enter into the stagnation with dysfunction and deteriorate tissue microenvironment in degenerative discs, which is recognized as cell senescence. During aging, many intrinsic and extrinsic factors have been proved to have strong connections with these cellular senescence phenomena. Growing evidences of these connections require us to gather up critical cues from potential risk factors to pathogenesis and relative interventions for retarding cell senescence and attenuating degenerative changes. In this paper, we try to clarify another important cell state apart from cell death in IDD and discuss senescence-associated changes in cells and extracellular microenvironment. Then, we emphasize the role of oxidative stress and epigenomic perturbations in linking risk factors to cell senescence in the onset of IDD. Further, we summarize the current interventions targeting senescent cells that may exert the benefits of antidegeneration in IDD.

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Autophagic Degradation of Gasdermin D Protects against Nucleus Pulposus Cell Pyroptosis and Retards Intervertebral Disc Degeneration In Vivo

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5584447 ◽

2021 ◽

Vol 2021 ◽

pp. 1-22

Author(s):

Zhiwei Liao ◽

Suyun Li ◽

Rong Liu ◽

Xiaobo Feng ◽

Yunsong Shi ◽

...

Keyword(s):

Cell Death ◽

Intervertebral Disc ◽

Nucleus Pulposus ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

Degradation Mechanism ◽

Nucleus Pulposus Cell ◽

Social Burden ◽

Related Proteins

Intervertebral disc degeneration (IDD) is the primary culprit of low back pain and renders heavy social burden worldwide. Pyroptosis is a newly discovered form of programmed cell death, which is also involved in nucleus pulposus (NP) cells during IDD progression. Moderate autophagy activity is critical for NP cell survival, but its relationship with pyroptosis remains unknown. This study is aimed at investigating the relationship between autophagy and pyroptotic cell death. The pyroptosis executor N-terminal domain of gasdermin D (GSDMD-N) and inflammation-related proteins were measured in lipopolysaccharide- (LPS-) treated human NP cells. Inhibition of autophagy by siRNA transfection and chemical drugs aggravated human NP cell pyroptosis. Importantly, we found that the autophagy-lysosome pathway and not the proteasome pathway mediated the degradation of GSDMD-N as lysosome dysfunction promoted the accumulation of cytoplasmic GSDMD-N. Besides, P62/SQSTM1 colocalized with GSDMD-N and mediated its degradation. The administration of the caspase-1 inhibitor VX-765 could reduce cell pyroptosis as confirmed in a rat disc IDD model in vivo, whereas ATG5 knockdown significantly accelerated the progression of IDD. In conclusion, our study indicated that autophagy protects against LPS-induced human NP cell pyroptosis via a P62/SQSTM1-mediated degradation mechanism and the inhibition of pyroptosis retards IDD progression in vivo. These findings deepen the understanding of IDD pathogenesis and hold implications in unraveling therapeutic targets for IDD treatment.

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Cell death in intervertebral disc degeneration

APOPTOSIS ◽

10.1007/s10495-013-0839-1 ◽

2013 ◽

Vol 18 (7) ◽

pp. 777-785 ◽

Cited By ~ 130

Author(s):

Fan Ding ◽

Zeng-wu Shao ◽

Li-ming Xiong

Keyword(s):

Cell Death ◽

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration

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Faculty Opinions recommendation of Novel function of TWEAK in inducing intervertebral disc degeneration.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1095070.550070 ◽

2007 ◽

Author(s):

Helen Gruber

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration

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INTERVERTEBRAL DISC DEGENERATION LINKED TO STRUCTURAL GENE VARIATIONS

Pakistan Journal of Medicine and Dentistry ◽

10.36283/pjmd8-4/012 ◽

2019 ◽

Author(s):

Saeeda Baig

Keyword(s):

Intervertebral Disc ◽

Disc Degeneration ◽

Intervertebral Disc Degeneration ◽

English Language ◽

Tandem Repeats ◽

Lumbar Disc ◽

Disease Process ◽

Nucleotide Polymorphisms ◽

Structural Protein ◽

Lumbar Disc Degeneration

During the recent past focus has shifted from identifying intervertebral disc degeneration as being caused by physical exposure and strain to being linked with a variety of genetic variations. The objective of this review is to provide an up to date review of the existing research data regarding the relation of intervertebral disc degeneration to structural protein genes and their polymorphisms and thus help clearly establish further avenues where research into causation and treatment is needed. A comprehensive search using the keywords “Collagen”, “COL”, “Aggrecan”, “AGC”, “IVDD”, “intervertebral disc degeneration”, and “lumbar disc degeneration” from PubMed and Google Scholar, where literature in the English language was selected spanning from 1991 to 2019. There are many genes involved in the production of structural components of an intervertebral disc. The issues in production of these components involve the over-expression or under-expression of their genes, and single nucleotide polymorphisms and variable number of tandem repeats affecting their structures. These structural genes include primarily the collagen and the aggrecan genes. While genetic and environmental factors all come into play with a disease process like disc degeneration, the bulk of research now shows the significantly larger impact of hereditary over exposure. While further research is needed into some of the lesser studied genes linked to IVDD and also the racial variations in genetic makeup, the focus in the near future should be on establishment of genetic testing to identify individuals at greater risk of disease and deliberation regarding the use of gene therapy to prevent disc degeneration.

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