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.

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.

Association between Measures of Vertebral Endplate Morphology and Lumbar Intervertebral Disc Degeneration

2017 ◽  
Vol 68 (2) ◽  
pp. 210-216 ◽  
Author(s):  
Semra Duran ◽  
Mehtap Cavusoglu ◽  
Hatice Gul Hatipoglu ◽  
Deniz Sozmen Cılız ◽  
Bulent Sakman
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Lumbar Disc ◽  
Lumbar Disc Degeneration ◽  
Vertebral Endplate ◽  
Lumbar Intervertebral Disc ◽  
Sagittal Diameter ◽  
Magnetic Resonance Imaging Mri ◽  
Vertebral Endplates

Purpose The aim of this study was to evaluate the association between vertebral endplate morphology and the degree of lumbar intervertebral disc degeneration via magnetic resonance imaging (MRI). Methods In total, 150 patients who met the inclusion criteria and were 20–60 years of age were retrospectively evaluated. Patients were evaluated for the presence of intervertebral disc degeneration or herniation, and the degree of degeneration was assessed at all lumbar levels. Vertebral endplate morphology was evaluated based on the endplate sagittal diameter, endplate sagittal concave angle (ECA), and endplate sagittal concave depth (ECD) on sagittal MRI. The association between intervertebral disc degeneration or herniation and endplate morphological measurements was analysed. Results In MRI, superior endplates ( ie, inferior endplates of the superior vertebra) were concave and inferior endplates ( ie, superior endplates of the inferior vertebra) were flat at all disc levels. A decrease in ECD and an increase in ECA were detected at all lumbar levels as disc degeneration increased ( P < .05). At the L4-L5 and L5-S1 levels, a decrease in ECD and an increase in ECA were detected in the group with herniated lumbar discs ( P < .05). There was no association between lumbar disc degeneration or herniation and endplate sagittal diameter at lumbar intervertebral levels ( P > .05). At all levels, ECD of women was significantly lesser than that of men and ECA of women was significantly greater than that of men ( P < .05). Conclusions There is an association between vertebral endplate morphology and lumbar intervertebral disc degeneration. Vertebral endplates at the degenerated disc level become flat; the severity of this flattening is correlated with the degree of disc degeneration.

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 Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF-α and Smad Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shaoyi Wang ◽  
Jianlu Wei ◽  
Jie Shi ◽  
Qiting He ◽  
Xiaocong Zhou ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Inflammatory Diseases ◽  
Morphological Changes ◽  
Intervertebral Discs ◽  
Inflammatory Factors ◽  
Wild Type ◽  
Tnf Α

Background. Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases. Objectives. The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression. Methods. We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting. Results. In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF-α-induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65. Conclusion. Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF-α response and Smad pathway activity and ultimately delayed IDD.

scholarly journals Protective Effect of Polygonatum sibiricum Polysaccharides on Apoptosis, Inflammation, and Oxidative Stress in Nucleus Pulposus Cells of Rats with the Degeneration of the Intervertebral Disc

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Zhaohui Zhai ◽  
Zhaoxin Li ◽  
Zhonglei Ji ◽  
Xiaosheng Lu
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Rat Model ◽  
Intervertebral Disc Degeneration ◽  
Intervertebral Discs ◽  
New Drugs ◽  
Nucleus Pulposus Cells ◽  
And Oxidative Stress

Objective. Polygonatum sibiricum polysaccharide (PSP) has antioxidant activity, immune enhancement, and other biological properties. However, the effect of PSP on intervertebral disc degeneration has not been reported. In this study, we mainly investigated the effect of PSP on the apoptosis, inflammation, and oxidative stress of nucleus pulposus cells (NPCs) during the process of intervertebral disc degeneration. Methods. A rat NPC model induced by H2O2 was constructed. The CCK8 method was used to measure the effects of PSP on the apoptosis of rat NPCs induced by H2O2. The effects on the activity of SOD and content of MDA were also determined. The rat model of intervertebral disc degeneration was treated with PSP for 1 month, and the mRNA expression levels of IL-1β, COX2, iNOS, Col2α1, Col10α1, and MMP3 were measured by qPCR in the tissue of intervertebral disc. NPCs from the degenerated intervertebral discs were separated, and the cell viability was measured by the CCK8 method. The contents of SOD and MDA in NPCs were determined as well. Results. PSP significantly reduced the apoptosis of NPCs induced by H2O2, significantly increased the SOD content, and decreased the content of MDA in H2O2-induced NPCs. The expression level of IL-1β, COX2, and iNOS in the rat model with intervertebral disc degeneration was significantly downregulated after 1 month of PSP treatment. PSP treatment increased the expression of Col2α1 type and significantly decreased the expression of Col10α1 type collagen and MMP3 in rats with disc degeneration. PSP treatment significantly reduced NPC apoptosis and increased its SOD content and reduced MDA content, which is consistent with the results from cell-level experiments. Conclusion. PSP can effectively reduce the apoptosis, inflammation, and oxidative stress of H2O2-induced NPCs in rats with intervertebral disc degeneration and mitigate the progression of intervertebral disc degeneration, which has the potential to be developed as new drugs for the treatment of intervertebral disc degeneration.

Effect of hyperglycemia on apoptosis of notochordal cells and intervertebral disc degeneration in diabetic rats

2009 ◽  
Vol 11 (6) ◽  
pp. 741-748 ◽  
Author(s):  
Ho-Yeon Won ◽  
Jong-Beom Park ◽  
Eun-Young Park ◽  
K. Daniel Riew
Keyword(s):  
Diabetes Mellitus ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Lumbar Disc ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Etiologic Factor ◽  
Notochordal Cells ◽  
Oletf Rats ◽  
Apoptosis Index

Object Diabetes mellitus is thought to be an important etiologic factor in intervertebral disc degeneration. It is known that notochordal cells gradually disappear from the nucleus pulposus (NP) of the intervertebral disc with age by undergoing apoptosis. What is not known is whether diabetes has an effect on apoptotic rates of notochordal cells. The purpose of this study was to investigate the effect of hyperglycemia on apoptosis of notochordal cells and intervertebral disc degeneration in age-matched OLETF (diabetic) and LETO (control) rats. Methods Lumbar disc tissue (L1–2 through L5–6), including cranial and caudal cartilaginous endplates, was obtained from 6- and 12-month-old OLETF and LETO rats (40 rats, 10 in each of the 4 groups). The authors examined the NP using TUNEL, histological analysis, and Western blot for expression of matrix metalloproteinase (MMP)–1, -2, -3, and -13, tissue inhibitor of metalloproteinase (TIMP)–1 and -2, and Fas (apoptosis-related protein). The apoptosis index of notochordal cells was calculated. The degree of transition of notochordal NP to fibrocartilaginous NP was classified on a scale ranging from Grade 0 (no transition) to Grade 4 (transition > 75%). The degree of expression of MMP-1, -2, -3, and -13, TIMP-1 and -2, and Fas was evaluated by densitometry. Results At 6 and 12 months of age, OLETF rats showed increased body weight and abnormal 2-hour glucose tolerance tests compared with LETO rats. The apoptosis index of notochordal cells was significantly higher in the OLETF rats than in the LETO rats at both 6 and 12 months of age. The degree of transition of notochordal NP to fibrocartilaginous NP was significantly higher in the OLETF rats than in the LETO rats at 6 and 12 months of age. The expression of MMP-1, -2, -3, and -13, TIMP-1, and Fas was higher in the OLETF rats at 6 and 12 months of age. The expression of TIMP-2 was significantly higher in the OLETF rats than in the LETO rats at 6 months of age, but not at 12. Conclusions The findings suggest that diabetes is associated with premature, excessive apoptosis of NP notochordal cells. This results in an accelerated transition of a notochordal NP to a fibrocartilaginous NP, which leads to early intervertebral disc degeneration. It remains to be determined if these premature changes are due to hyperglycemia or some other factors associated with diabetes. Understanding the mechanism by which diabetes affects disc degeneration is the first step in designing therapeutic modalities to delay or prevent disc degeneration caused by diabetes mellitus.

scholarly journals Propionibacterium acnes Induces Intervertebral Disc Degeneration by Promoting iNOS/NO and COX-2/PGE2 Activation via the ROS-Dependent NF-κB Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yazhou Lin ◽  
Guoqing Tang ◽  
Yucheng Jiao ◽  
Ye Yuan ◽  
Yuehuan Zheng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Propionibacterium Acnes ◽  
Intervertebral Discs ◽  
Cox 2 ◽  
Underlying Mechanisms

Accumulating evidence suggests that Propionibacterium acnes (P. acnes) is a novel pathogenic factor promoting intervertebral disc degeneration (IVDD). However, the underlying mechanisms by which P. acnes induces IVDD have been unclear. In this study, we quantified the severity of IVDD, as well as the expressions of inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase (COX-2)/prostaglandin (PGE2) in human intervertebral discs (IVDs) infected with P. acnes. Compared with P. acnes-negative IVDs, P. acnes-positive IVDs showed increased iNOS/NO and COX-2/PGE2 activity concomitant with more severe IVDD. In order to detect the potential correlation between iNOS/NO expression, COX-2/PGE2 expression, and IVDD, we developed a P. acnes-induced IVDD rat model and found that the upregulation of iNOS/NO and COX-2/PGE2 was essential to the occurrence of P. acnes-induced IVDD. This finding was supported by the fact that the inhibition of iNOS/NO and COX-2/PGE2 activity ameliorated IVDD significantly, as evidenced by restored aggrecan and collagen II expression both in vivo and in vitro. Mechanistically, we found that P. acnes induced iNOS/NO and COX-2/PGE2 expressions via a reactive oxygen species- (ROS-) dependent NF-κB cascade. Furthermore, NADPH oxidase participated in P. acnes-induced ROS, iNOS/NO, and COX-2/PGE2 expressions. Overall, these findings further validated the involvement of P. acnes in the pathology of IVDD and provided evidence that P. acnes-induced iNOS/NO and COX-2/PGE2 activation via the ROS-dependent NF-κB pathway is likely responsible for the pathology of IVDD.

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