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.

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 The Myth of Fibroid Degeneration in the Canine Intervertebral Disc: A Histopathological Comparison of Intervertebral Disc Degeneration in Chondrodystrophic and Nonchondrodystrophic Dogs

2017 ◽  
Vol 54 (6) ◽  
pp. 945-952 ◽  
Author(s):  
Tove Hansen ◽  
Lucas A. Smolders ◽  
Marianna A. Tryfonidou ◽  
Björn P. Meij ◽  
Johannes C. M. Vernooij ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Histopathological Changes ◽  
Seminal Work ◽  
Notochordal Cells ◽  
Tissue Changes ◽  
Chondroid Metaplasia ◽  
Ivd Degeneration

Since the seminal work by Hans-Jörgen Hansen in 1952, it has been assumed that intervertebral disc (IVD) degeneration in chondrodystrophic (CD) dogs involves chondroid metaplasia of the nucleus pulposus, whereas in nonchondrodystrophic (NCD) dogs, fibrous metaplasia occurs. However, more recent studies suggest that IVD degeneration in NCD and CD dogs is more similar than originally thought. Therefore, the aim of this study was to compare the histopathology of IVD degeneration in CD and NCD dogs. IVDs with various grades of degeneration (Thompson grade I–III, n = 7 per grade) from both CD and NCD dogs were used (14 CD and 18 NCD dogs, 42 IVDs in total). Sections were scored according to a histological scoring scheme for canine IVD degeneration, including evaluation of the presence of fibrocyte-like cells in the nucleus pulposus. In CD dogs, the macroscopically non-degenerated nucleus pulposus contained mainly chondrocyte-like cells, whereas the non-degenerated nucleus pulposus of NCD dogs mainly contained notochordal cells. The histopathological changes in degenerated discs were similar in CD and NCD dogs and resembled chondroid metaplasia. Fibrocytes were not seen in the nucleus pulposus, indicating that fibrous degeneration of the IVD was not present in any of the evaluated grades of degeneration. In conclusion, intervertebral disc degeneration was characterized by chondroid metaplasia of the nucleus pulposus in both NCD and CD dogs. These results revoke the generally accepted concept that NCD and CD dogs suffer from a different type of IVD degeneration, in veterinary literature often referred to as chondroid or fibroid degeneration, and we suggest that chondroid metaplasia should be used to describe the tissue changes in the IVD in both breed types.

scholarly journals Yiqi Huoxue Recipe Delayed Intervertebral Disc Degeneration by Activating Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Feng Dai ◽  
Pengfei Yu ◽  
Zhenhan Yu ◽  
Hong Jiang ◽  
Zhijia Ma ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Lumbar Disc ◽  
Inflammatory Factors ◽  
Transmission Electron ◽  
Histopathologic Analysis ◽  
Related Proteins ◽  
First Time ◽  
Related Pathway

Autophagy has been proved to occur in rats with intervertebral disc degeneration (IVDD). Yiqi Huoxue recipe (YQHXR), an effective therapy of traditional Chinese medicine, was widely used for ruptured lumbar disc herniation under clinical observation. More importantly, YQHXR positively regulated the expression of autophagy-related proteins. However, little is known about the significance of YQHXR in the pathologic process of IVDD. Therefore, this study explored the protective effect of YQHXR based on IVDD rat model through magnetic resonance imaging and histopathologic analysis. Then we evaluated the formation of autophagosomes in the degenerated intervertebral disc by transmission electron microscope. Real-time PCR was used to detect the changes of autophagy-related genes. Western blot and immunoprecipitation were used to assess the protein expression of the autophagy-related pathway. We found that YQHXR-induced autophagy attenuated the release of inflammatory factors. In addition, YQHXR promoted the formation of Beclin1-VPS34 complex to activate autophagy through not only activation of the upstream protein AMPK and upregulation of the deubiquitinase USP13, thus in turn alleviating the development of IVDD. We proposed the potential molecular mechanism of YQHXR on autophagy for the first time, so as to provide a theoretical and experimental basis for the clinical application of YQHXR in the treatment of IVDD-related diseases.

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 Platelet-Derived Biomaterials Exert Chondroprotective and Chondroregenerative Effects on Diabetes Mellitus-Induced Intervertebral Disc Degeneration

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1054
Author(s):  
Wen-Cheng Lo ◽  
Chun-Chao Chang ◽  
Chun-Hao Chan ◽  
Abhinay Kumar Singh ◽  
Yue-Hua Deng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Transforming Growth Factor ◽  
Disc Height ◽  
Therapeutic Effects

Complications of diabetes mellitus (DM) range from acute to chronic conditions, leading to multiorgan disorders such as nephropathy, retinopathy, and neuropathy. However, little is known about the influence of DM on intervertebral disc degeneration (IVDD). Moreover, traditional surgical outcomes in DM patients have been found poor, and to date, no definitive alternative treatment exists for DM-induced IVDD. Recently, among various novel approaches in regenerative medicine, the concentrated platelet-derived biomaterials (PDB), which is comprised of transforming growth factor-β1 (TGF-β1), platelet-derived growth factor (PDGF), etc., have been reported as safe, biocompatible, and efficacious alternatives for various disorders. Therefore, we initially investigated the correlations between DM and IVDD, through establishing in vitro and in vivo DM models, and further evaluated the therapeutic effects of PDB in this comorbid pathology. In vitro model was established by culturing immortalized human nucleus pulposus cells (ihNPs) in high-glucose medium, whereas in vivo DM model was developed by administering streptozotocin, nicotinamide and high-fat diet to the mice. Our results revealed that DM deteriorates both ihNPs and IVD tissues, by elevating reactive oxygen species (ROS)-induced oxidative stress, inhibiting chondrogenic markers and disc height. Contrarily, PDB ameliorated IVDD by restoring cellular growth, chondrogenic markers and disc height, possibly through suppressing ROS levels. These data imply that PDB may serve as a potential chondroprotective and chondroregenerative candidate for DM-induced IVDD.

Radiologic Analysis of Causes of Early Recurrence after Percutaneous Endoscopic Transforaminal Discectomy

2021 ◽  
Author(s):  
Zepeng Li ◽  
Lulu Liu ◽  
Hao Liu ◽  
Jinghua Tan ◽  
Xuelin Li ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Lumbar Disc Herniation ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Lumbar Disc ◽  
Early Recurrence ◽  
Tear Size ◽  
Base Width

Abstract Objective: To retrospectively analyze causes of, and factors influencing, early recurrence after percutaneous endoscopic transforaminal discectomy (PETD) used to treat lumbar-disc herniation. Methods: We included 285 patients with single-segment lumbar-disc herniation, treated using PETD from January 2017 to December 2019 in the First Affiliated Hospital of the University of South China. Patients were classified into early recurrence and non-early recurrence groups based on clinical symptoms and MRI reexamination. Differences in disc-height index (DHI), sagittal range of motion (sROM), base-width of intervertebral disc degeneration, and postoperative intervertebral annulus-fibrosus tear size were compared using independent-sample t test. Differences in degree of intervertebral disc degeneration and herniation sites were analyzed using rank-sum and chi-square tests. Logistic regression was used for multivariate analysis of factors associated with early recurrence after PETD. Results: Two hundred and eighty five patients completed surgery and underwent clinical follow-up. Mean follow-up duration was 15.5 months (12–24 months). During follow-up, 19 patients relapsed within 6 months post-surgery. Early recurrence rate was 6.7%, and mean recurrence duration was 73.4 days (3–168 days). Differences in DHI, base-width, postoperative annulus-fibrosus tear size, degree of intervertebral disc degeneration, and herniation sites between early recurrence and non-early recurrence groups were statistically significant (P<0.05). Herniation site and base-width of herniation were significantly correlated with early recurrence after PETD. Conclusions: DHI, postoperative annulus-fibrosus tear size, and degree of intervertebral disc degeneration were associated with early recurrence after PETD. Increased base-width of herniation was a risk factor for early recurrence after PETD. Central-herniation patients with were more prone to postoperative early recurrence than paracentral-herniation patients.

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