scholarly journals Excessive mechanical strain accelerates intervertebral disc degeneration by disrupting intrinsic circadian rhythm

2021 ◽  
Author(s):  
Sheng-Long Ding ◽  
Tai-Wei Zhang ◽  
Qi-Chen Zhang ◽  
Wang Ding ◽  
Ze-Fang Li ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Intervertebral Disc ◽  
Mechanical Loading ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Night Shift ◽  
Mechanical Strain ◽  
Inhibitory Effect ◽  
Shift Workers ◽  
Normal Environment

AbstractNight shift workers with disordered rhythmic mechanical loading are more prone to intervertebral disc degeneration (IDD). Our results showed that circadian rhythm (CR) was dampened in degenerated and aged NP cells. Long-term environmental CR disruption promoted IDD in rats. Excessive mechanical strain disrupted the CR and inhibited the expression of core clock proteins. The inhibitory effect of mechanical loading on the expression of extracellular matrix genes could be reversed by BMAL1 overexpression in NP cells. The Rho/ROCK pathway was demonstrated to mediate the effect of mechanical stimulation on CR. Prolonged mechanical loading for 12 months affected intrinsic CR genes and induced IDD in a model of upright posture in a normal environment. Unexpectedly, mechanical loading further accelerated the IDD in an Light-Dark (LD) cycle-disrupted environment. These results indicated that intrinsic CR disruption might be a mechanism involved in overloading-induced IDD and a potential drug target for night shift workers.

The inhibitory effect of salmon calcitonin on intervertebral disc degeneration in an ovariectomized rat model

2014 ◽  
Vol 24 (8) ◽  
pp. 1691-1701 ◽  
Author(s):  
Yang Luo ◽  
Liu Zhang ◽  
Wen-Ya Wang ◽  
Qi-Feng Hu ◽  
Hui-Ping Song ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Rat Model ◽  
Salmon Calcitonin ◽  
Intervertebral Disc Degeneration ◽  
Inhibitory Effect ◽  
Ovariectomized Rat

scholarly journals Reducing Inflammation and Vascular Invasion in Intervertebral Disc Degeneration via Cystathionine-γ-Lyase Inhibitory Effect on E-Selectin

2021 ◽  
Vol 9 ◽  
Author(s):  
Haoran Xu ◽  
Kang Wei ◽  
Jingyao Tu ◽  
Yangmengfan Chen ◽  
Yi He ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Vascular Function ◽  
Vascular Invasion ◽  
Intervertebral Disc Degeneration ◽  
Human Life ◽  
Lumbar Disc ◽  
Inhibitory Effect ◽  
Intervertebral Discs ◽  
Spinal Diseases

The incidence of degenerative spinal diseases, such as cervical spondylosis and thoracic and lumbar disc herniation, is increasing. These health problems have adversely affected human life and work. Surgical intervention is effective when intervertebral disc degeneration (IDD) causes nerve compression and/or severely limits daily activity. Early IDD patients generally do not require surgery. However, there is no effective method of impeding IDD progression. Thus, novel approaches to alleviating IDD deterioration are urgently required. Cystathionine-γ-lyase (CSE) and E-selectin (CD62E) are vital factors regulating vascular function and inflammation. However, their effects on IDD and vascular invasion in intervertebral discs (IVDs) are pending further exploration. Here, bioinformatics and human nucleus pulposus (NP) tissues analyses revealed that CSE was significantly downregulated and CD62E was upregulated in the NP tissues of IDD patients. We demonstrated that CSE overexpression, CD62E downregulation, and NF-κB (P65) inhibition mitigate inflammation and recover metabolic function in NP cells. Similarly, CSE attenuated vascular invasion induced by inflammatory irritation. Using a rat IDD model, we showed that CSE improved degeneration, inflammation, and microvascular invasion in NP tissue, whereas CD62E had the opposite effect. Taken together, our results indicated that the CSE/CD62E pathway could effectively improve the inflammatory environment and vascular invasion in IVD. Hence, the findings of this study propose a promising and valuable strategy for the treatment of patients with early IDD as well as postoperative adjuvant therapy in patients with severe IDD.

scholarly journals Metformin alleviates intervertebral disc degeneration by upregulating MMP-1 expression via the KDM6A/SOX9/miR-202-3p/MMP-1 signaling pathway

2021 ◽  
Author(s):  
Xin-yao Hu ◽  
Dong-zi Cao ◽  
Zhi-hua Wang
Keyword(s):  
Intervertebral Disc ◽  
Signaling Pathway ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Methylation Status ◽  
Inhibitory Effect ◽  
Luciferase Assay ◽  
Downstream Target ◽  
Neuronal Precursor Cells

IntroductionMiR-202-3p is involved in the pathogenesis of intervertebral disc degeneration (IDD) via regulating MMP-1 expression in neuronal precursor cells (NPCs). As an activator of miR-202-3p and KDM6A expression, metformin (MET) may regulate the expression of SOX9 via regulating the methylation status of SOX9 promoter. However, the role of MET in the treatment of IDD remains to be explored.Material and methodsQuantitative real-time PCR was performed to analyze the expression of KDM66, SOX9, MMP-1 and miR-202-3p in NPCs and IDD rabbits. Western blot was carried out to evaluate the expression of KDM6A, SOX9 and MMP-1 protein under different conditions. Bisulfite sequencing PCR was used to analyze the DNA methylation of SOX9 promoter. Luciferase assay was carried out to explore the inhibitory effect of miR-202-3p upon MMP-1.ResultsThe expression of KDM6A, SOX9 and MMP-1 was abnormal in IDD cells and rabbits, while the MET treatment restored the normal expression of KDM6A, SOX9 and MMP-1 and miR-202-3p. Mechanistically, MET treatment reduced the level of hypermethylation of SOX9 promoter, thus restoring the expression of SOX9 in IDD cells and rabbits. The elevation in SOX9 expression promoted the expression of miR-202-3p, therefore inhibiting the expression of MMP-1, a downstream target of miR-202-3p.ConclusionsIn this study, we set up cellular and animal models of IDD and treated them with MET to probe the effect of MET on IDD and the signaling pathway of KDM6A/SOX9/miR-202-3p/MMP-1. Our work provided deep insight into the molecular mechanism underlying the therapeutic role of MET in the treatment of IDD.

INTERVERTEBRAL DISC DEGENERATION LINKED TO STRUCTURAL GENE VARIATIONS

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.

The Caspase-3 Knockout Inhibits Intervertebral Disc Degeneration Related to Injury But Accelerates Degeneration Related to Aging

2019 ◽  
Author(s):  
Takashi Ohnishi ◽  
Katsuhisa Yamada ◽  
Koji Iwasaki ◽  
Takeru Tsujimoto ◽  
Hideaki Higashi ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Caspase 3

Inhibition of LRRK2 Restores Parkin-Mediated Mitophagy and Suppresses Apoptosis in Intervertebral Disc Degeneration

2020 ◽  
Author(s):  
Jialiang Lin ◽  
Xuanqi Zheng ◽  
Zengjie Zhang ◽  
Zhenxuan Shao ◽  
Chongan Huang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration
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