Verification of a Numerical Model for Simulating Intervertebral Disc Pathophysiology

2020 ◽  
Author(s):  
Xin Gao ◽  
Weiyong Gu
Keyword(s):  
Intervertebral Disc ◽  
Computational Model ◽  
Disc Degeneration ◽  
Excellent Agreement ◽  
Convergence Rates ◽  
Numerical Solutions ◽  
The United States ◽  
Benchmark Problems ◽  
Manufactured Solutions ◽  
Ivd Degeneration

Abstract Intervertebral disc (IVD) degeneration may cause low back pain which has a tremendous impact on the society and economy in the United States. It is important to quantitatively and qualitatively evaluate its pathophysiology in order to diagnose and treat disc degeneration. Recently, we have developed a multiphasic computational model for investigating cell mediated disc degeneration as well as exploring new strategies for disc therapies. The objective of this study was to verify this new computational model according to the guidelines of ASME V&V40. The model was discretized with finite element method and implemented in COMSOL Multiphysics. Several benchmark problems and method of manufactured solutions (MMS) were used to verify the numerical implementation. For all the benchmark problems tested, the numerical results were in excellent agreement with those analytical solutions or other numerical solutions. In addition, the observed convergence rates of primary unknowns obtained with MMS were in excellent agreement with theoretical convergence rates. This study showed that our model has been verified and found no evidence of coding errors.

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 Inhibition of aberrant Hif1α activation delays intervertebral disc degeneration in adult mice

Bone Research ◽  
2022 ◽  
Vol 10 (1) ◽  
Author(s):  
Zuqiang Wang ◽  
Hangang Chen ◽  
Qiaoyan Tan ◽  
Junlan Huang ◽  
Siru Zhou ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Genetic Ablation ◽  
Adult Mice ◽  
Conditional Deletion ◽  
Current Therapies ◽  
Cartilaginous Endplate ◽  
Ivd Degeneration ◽  
Deficient Mice

AbstractThe intervertebral disc (IVD) is the largest avascular tissue. Hypoxia-inducible factors (HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease (DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate (EP) and annulus fibrosus (AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. Aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol (2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

scholarly journals Mesenchymal Stem Cell for Prevention and Management of Intervertebral Disc Degeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Umile Giuseppe Longo ◽  
Nicola Papapietro ◽  
Stefano Petrillo ◽  
Edoardo Franceschetti ◽  
Nicola Maffulli ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Surgical Intervention ◽  
Pathological Condition ◽  
Treatment Strategies ◽  
Clinical Applications ◽  
Ivd Degeneration

Intervertebral disc degeneration (IVD) is a frequent pathological condition. Conservative management often fails, and patients with IVD degeneration may require surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. The aim of biological strategies is to prevent and manage IVD degeneration, improve the function, the anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells, and inhibit matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of mesenchymal stem cells and gene therapy for the prevention and treatment of IVD degeneration.

Developing consistently reproducible intervertebral disc degeneration at rat caudal spine by using needle puncture

2009 ◽  
Vol 10 (6) ◽  
pp. 522-530 ◽  
Author(s):  
Huina Zhang ◽  
Frank La Marca ◽  
Scott J. Hollister ◽  
Steven A. Goldstein ◽  
Chia-Ying Lin
Keyword(s):  
Animal Model ◽  
Mr Imaging ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Collagen Type ◽  
Type Ii ◽  
Collagen Type Ii ◽  
Anulus Fibrosus ◽  
Safranin O ◽  
Ivd Degeneration

Object The goal in this study was to develop a convenient, less-invasive animal model to monitor progression of intervertebral disc (IVD) degeneration for future testing of new treatments for disc degeneration. Methods Level 5/6 and 7/8 IVDs of rat caudal spine were stabbed laterally with 18- or 21-gauge hypodermic needles to a depth of 5 mm from the subcutaneous surface with the aid of fluoroscopy. In vivo MR imaging studies were performed at 4, 8, and 12 weeks postsurgery to monitor progression of IVD degeneration. Histological analysis including H & E and safranin O staining, and immunohistochemical studies of collagen type II and bone morphogenetic protein receptor type II (BMPRII) were assessed at 12 weeks postsurgery. Results The 18- and 21-gauge needle–stabbed discs illustrated decreases in both the T2 density and MR imaging index starting at 4 weeks, with no evidence of spontaneous recovery by 12 weeks. Histological staining demonstrated a decreased nucleus pulposus (NP) area, and the NP–anulus fibrosus border became unclear during the progression of disc degeneration. Similar patterns of degenerative signs were also shown in both safranin O– and collagen type II–stained sections. The BMPRII immunohistochemical analysis of stabbed discs demonstrated an increase in BMPRII expression in the remaining NP cells and became stronger in anulus fibrosus with the severity of disc degeneration. Conclusions After introducing an 18- or 21-gauge needle into the NP area of discs in the rat tail, the stabbed disc showed signs of degeneration in terms of MR imaging and histological outcome measurements. Changes in BMPRII expression in this animal model provide an insight for the effectiveness of delivering BMPs into the region responsible for chondrogenesis for disc repair. This convenient, less-invasive, reproducible, and cost-effective model may be a useful choice for testing novel treatments for disc degeneration.

scholarly journals The Upregulation of COX2 in Human Degenerated Nucleus Pulposus: The Association of Inflammation with Intervertebral Disc Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Chang Liu ◽  
Guoyan Liang ◽  
Zhantao Deng ◽  
Jing Tan ◽  
Qiujian Zheng ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Cell Number ◽  
Total Cell ◽  
Smoking History ◽  
Total Cell Number ◽  
Baseline Information ◽  
Ivd Degeneration ◽  
Cell Cell

Intervertebral disc degeneration (IVDD) is an important risk factor of low back pain. We previously found upregulated markers of fibrosis, the late stage of chronic inflammation, in degenerated IVD with a small number of clinical specimens. Here, we aimed to study on a larger scale the association of cyclooxygenase 2 (COX2), an inflammation and/or pain marker, with IVDD. This study involved 107 LBP participants. The IVD degeneration level was graded on a 1–5 scale according to the Pfirrmann classification system. Discs at grades 1-3 were further grouped as white discs with grades 4-5 as black discs. We recorded baseline information about age, gender, body mass index (BMI), diabetes history, smoking history, and magnetic resonance imaging (MRI). Their association with IVDD was statistically analyzed. The expression level of COX2 was investigated by immunohistochemistry. The total integrated COX2 optical density (IOD), number of COX2-positive cells, and total cell number of each image were counted and analyzed by Image-Pro Plus software. The IOD and number of COX2-positive cells were divided by the total cell number to obtain COX2 expression density (IOD/cell) and COX2 positivity (cell+/cell). As a result, among the baseline information investigated, only age was found to have a significant association with IVDD. The IOD/cell was found to be significantly increased from grade 2 to grade 5, as well as in black discs compared to white discs. The cell+/cell displayed the same trend that it increased in highly degenerative discs compared to their counterparts. In conclusion, the expression of COX2 is associated with IVDD, which highlights COX2 as a biomarker for IVD degeneration and indicates the involvement of inflammation and pain signaling in IVDD.

scholarly journals Stem Cells and Exosomes: New Therapies for Intervertebral Disc Degeneration

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2241
Author(s):  
Zoe Krut ◽  
Gadi Pelled ◽  
Dan Gazit ◽  
Zulma Gazit
Keyword(s):  
Stem Cell ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Financial Burden ◽  
The United States ◽  
Mechanical Trauma ◽  
Disc Disease ◽  
Surgical Interventions ◽  
Symptomatic Disease

Intervertebral disc degeneration (IVDD) occurs as a result of an imbalance of the anabolic and catabolic processes in the intervertebral disc, leading to an alteration in the composition of the extracellular matrix (ECM), loss of nucleus pulposus (NP) cells, excessive oxidative stress and inflammation. Degeneration of the IVD occurs naturally with age, but mechanical trauma, lifestyle factors and certain genetic abnormalities can increase the likelihood of symptomatic disease progression. IVDD, often referred to as degenerative disc disease (DDD), poses an increasingly substantial financial burden due to the aging population and increasing incidence of obesity in the United States. Current treatments for IVDD include pharmacological and surgical interventions, but these lack the ability to stop the progression of disease and restore the functionality of the IVD. Biological therapies have been evaluated but show varying degrees of efficacy in reversing disc degeneration long-term. Stem cell-based therapies have shown promising results in the regeneration of the IVD, but face both biological and ethical limitations. Exosomes play an important role in intercellular communication, and stem cell-derived exosomes have been shown to maintain the therapeutic benefit of their origin cells without the associated risks. This review highlights the current state of research on the use of stem-cell derived exosomes in the treatment of IVDD.

scholarly journals Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Marion Fusellier ◽  
Pauline Colombier ◽  
Julie Lesoeur ◽  
Samy Youl ◽  
Stéphane Madec ◽  
...  
Keyword(s):  
Animal Models ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Enzyme Treatment ◽  
In Vivo Model ◽  
Regenerative Approach ◽  
Radiation Induced ◽  
Longitudinal Comparison ◽  
Ivd Degeneration

Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos’ scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos’ scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.

scholarly journals Lycorine Suppresses Endplate-Chondrocyte Degeneration and Prevents Intervertebral Disc Degeneration by Inhibiting NF-κB Signalling Pathway

2018 ◽  
Vol 45 (3) ◽  
pp. 1252-1269 ◽  
Author(s):  
Gangliang Wang ◽  
Kangmao Huang ◽  
Yangxin Dong ◽  
Shuai Chen ◽  
Jianfeng Zhang ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
High Performance ◽  
Underlying Mechanism ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Cell Degeneration ◽  
Ivd Degeneration ◽  
Protease Expression

Background/Aims: Cartilaginous endplate (CEP) degeneration is an important cause for intervertebral disc (IVD) degeneration that leads to low-back pain. The identification of compounds that may prevent CEP degeneration is of interest for the prevention of IVD degeneration. Methods: Catabolic protease expression in the CEP of disc degeneration patients was first assessed. The toxicity, function and underlying mechanism of lycorine (LY) on CEP-derived chondrocytes degeneration were assessed in vitro by flow cytometry analysis and western blotting. The concentration and function of LY in rat-tail disc-degeneration models were also assessed by HPLC (High Performance Liquid Chromatography) quantification and histological analysis. Results: In CEP cells, Interleukin (IL)-1β upregulated the expression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 that is critical for the degradation of cartilage extracellular matrix. Interestingly, LY suppressed the expression of these enzymes via the inhibition of nuclear factor-κB (NFκB) signalling and thus prevented IL-1β-induced endplate cell degeneration in vitro. More importantly, LY also reduced the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in CEP and exerted a protective effect on both CEP and nucleus pulposus (NP) degeneration. In addition to its inhibitory effect on matrix-degrading protease expression, LY treatment also reduced positive regulators of proinflammatory cytokines, such as MIF, which can be secreted by CEP cells and subsequently target NP cells. Conclusion: LY could serve as a potential drug for treating IVD disease.

scholarly journals Growth Factors and Anticatabolic Substances for Prevention and Management of Intervertebral Disc Degeneration

2012 ◽  
Vol 2012 ◽  
pp. 1-9
Author(s):  
Umile Giuseppe Longo ◽  
Stefano Petrillo ◽  
Edoardo Franceschetti ◽  
Nicola Maffulli ◽  
Vincenzo Denaro
Keyword(s):  
Growth Factors ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Intervertebral Disc Degeneration ◽  
Surgical Intervention ◽  
Treatment Strategies ◽  
Clinical Applications ◽  
Ivd Degeneration

Intervertebral disc (IVD) degeneration is frequent, appearing from the second decade of life and progressing with age. Conservative management often fails, and patients with IVD degeneration may need surgical intervention. Several treatment strategies have been proposed, although only surgical discectomy and arthrodesis have been proved to be predictably effective. Biological strategies aim to prevent and manage IVD degeneration, improving the function and anabolic and reparative capabilities of the nucleus pulposus and annulus fibrosus cells and inhibiting matrix degradation. At present, clinical applications are still in their infancy. Further studies are required to clarify the role of growth factors and anticatabolic substances for prevention and management of intervertebral disc degeneration.

Effects of Static Compression on Energy Metabolism of Porcine Intervertebral Disc

2010 ◽  
Author(s):  
Tai-Yi Yuan ◽  
Hanan N. Fernando ◽  
Jessica Czamanski ◽  
Chong Wang ◽  
Wei Yong Gu ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Intervertebral Disc ◽  
Lactate Concentration ◽  
The United States ◽  
Low Back ◽  
Static Compression ◽  
Cellular Energy ◽  
Tissue Integrity ◽  
Ivd Degeneration ◽  
Local Oxygen

Degeneration of the intervertebral disc (IVD) has been associated with low back pain, which is one of the major socio-economic problems in the United States. Since IVD is the largest avascular cartilaginous structure in the human body, poor nutrient supply has been suggested as a potential mechanism for IVD degeneration. Biosynthesis of extracellular matrix is an energy demanding process which is required to maintain tissue integrity [1]. Cells consume glucose and oxygen to produce adenosine triphosphate (ATP), the main energy form in cells. Glycolysis, the primary metabolic pathway for production of ATP in IVD cells, is strongly regulated by local oxygen concentration and pH (which is governed by lactate concentration) [2]. Therefore, energy metabolism may play an important role in the malnutrition pathway leading to IVD degeneration. The objective of this study was to investigate the effect of mechanical loading on cellular energy metabolism in whole disc and in agarose gels.

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