Genetic Alterations in Intervertebral Disc Disease

Martirosyan, Nikolay L.; Patel, Arpan; Carotenuto, Alessandro; Kalani, M. Yashar S.; Belykh, Evgenii; Walker, Corey T.; Preul, Mark C.; Theodore, Nicholas

doi:10.3389/fsurg.2016.00059

Cited by 101 publications

(88 citation statements)

References 63 publications

(208 reference statements)

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“…These include reduced water retention in the NP [5,7,8], increased percent of type I collagen within the NP and inner AF [9], degradation of collagen and extracellular matrix (ECM) materials [10], and upregulation of systems of degradation such as apoptosis, matrix metalloproteinase (MMP) expression, and inflammatory pathways [11].…”

Section: Pathology Of Ldhmentioning

confidence: 99%

“…It is estimated that the condition has approximately 75% heredity origin [12]. Genes that have been found to significantly increase risk of LDH include those encoding structural proteins, matrix metalloproteinases, apoptosis factors, growth factors, and single nucleotide polymorphisms in the vitamin D receptor gene resulting in inflammatory cytokine imbalance [11].…”

Section: Genetic Predispositionmentioning

confidence: 99%

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Lumbar Disc Herniation

Amin

Andrade

Neuman³

2017

Curr Rev Musculoskelet Med

243

202

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Purpose of Review Substantial advancements have been made in the cause, diagnosis, imaging, and treatment options available for patients with lumbar disc herniation (LDH). We examined the current evidence and highlight the concepts on the frontline of discovery in LDH. Recent Findings There are a myriad of novel etiologies of LDH detailed in recent literature including inflammatory factors and infectious microbes. In the clinical setting, recent data focuses on improvements in computer tomography as a diagnostic tool and non-traditional injection options including tumor necrosis alpha inhibitors and platelet-rich plasma. Operative treatment outcomes have focused on minimally invasive endoscopic approaches and demonstrated robust 5-year post-operative outcomes. Summary Advances in the molecular etiology of LDH will continue to drive novel treatment options. The role of endoscopic treatment for LDH will continue to evolve. Further research into10-year outcomes will be necessary as this surgical approach continues to gain widespread popularity.

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Section: Pathology Of Ldhmentioning

confidence: 99%

Section: Genetic Predispositionmentioning

confidence: 99%

Lumbar Disc Herniation

Amin

Andrade

Neuman³

2017

Curr Rev Musculoskelet Med

243

202

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“…Similarly increase in expression of ADAMTS (esp. ADAMTS-4 and -5 increases the aggrecan turnover) results in accelerated IVD degeneration [18]. MMP-3 are categorized as stromelysins which degrades proteoglycans, laminas and other components of ECM and indirectly degrades the disc by activating MMPs [18].…”

Section: Matrix Degrading Enzymes and Catabolic Mediatorsmentioning

confidence: 99%

“…collagen II and proteoglycan molecules [21]. Research suggests that SNPs in both COL11A2 and COL11A1 could predispose an individual to an increased risk of developing IVD degeneration [18]. VDR was the first reported gene associated with IVD degeneration in a Finnish study with alleles Taq1 and Fok1 polymorphism being associated with reduced signals on magnetic resonance Imaging (MRI) of thoracic and lumbar disc [29].…”

Section: Genetic Influence On Ivd Degenerationmentioning

confidence: 99%

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Etiology and Risk Factors of Lumbar Intervertebral Disc (IVD) Degeneration

Debnath¹

2018

RMES

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Biological factors (Table 1) Changes in ECM (Extracellular Matrix): Collagen synthesis increases in the initial stages of degeneration with a clear increase in type II Collagen in the NP (maybe indicating repair mechanism) [9]. As the degeneration progresses the synthesis pattern changes and more type II Collagen is synthesized in AF. Type I collagen is synthesized in the deep region of AF and NP. Type X collagen formation is associated with chondrocyte agglomerates and tears of degenerated IVDs. The synthesis of proteoglycans also changes with decline in production of aggrecan and increase in the synthesis of versican, biglycan and decorin. There is reduced Glycosaminoglycans (GAGs) esp. modification of chondroitin sulfate to keratan sulfate. These results in disc desiccation and degeneration [10]. The remodeling of the ECM results from these changes occurring simultaneously. The protagonists of the process are the matrix metallo-proteinases (MMPs) [11]. There are ADAMTS (a desintegrin and metalloproteinase with thrombospondin), which play similar but more powerful roles like MMPs. Both these families have the same endogenous inhibitors called TIMPs (Tissue inhibitor matrix metallo-proteinases), which act synergistically in the remodeling of ECM [12]. Review Article Research in Medical & Engineering Sciences C CRIMSON PUBLISHERS Wings to the Research 1/10Copyright © All rights are reserved by Ujjwal K Debnath. Volume 4 -Issue 5 ISSN: 2576-8816 AbstractLumbar degenerative disc disease (DDD) is a progressive condition that exists along a continuum of pathologic processes. The disease starts as desiccation of the nucleus pulposus, to annular tearing, diffuse disc bulging, and disc space collapse, the degenerative process can occur over the course of decades, culminating in substantial debilitation. Clinically DDD presents with back pain and/or radiculopathy, can limit work and productivity. Additionally, the cost of treating this condition is especially high, and billions of dollars are spent on managing degenerative spinal processes annually.In this review, the main focus is on the recent advances in studies on the most extensively examined risk factors and genetic factors associated with DDD in humans. A number of genetic defects have been correlated with structural and functional changes within the intervertebral disc (IVD), which may compromise the disc's mechanical properties and metabolic activities. These studies have begun to shed light on the molecular basis of DDD, suggesting that genetic factors are important contributors to the onset and progression of IDD. By continuing to improve our understanding of the molecular mechanisms of DDD, specific early diagnosis and more effective treatments for this disabling disease may be possible in the future. Res Med Eng Sci 2/10How Proinflammatory cytokinesMost important cytokines which influences the IVD degeneration process are Interleukin -1 (IL-1) and Tumor necrosis factor-α (TNF-α). Large volumes of research and evidence suggest these cytokines are directly ...

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Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2

Zhang

et al. 2021

Cell Biology International

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P53 is an apoptosis marker which is involved in determining nucleus pulposus (NP) cell fate. Little is known about P53 interaction with N‐Myc downstream‐regulated gene 2 (NDRG2) in intervertebral disc degeneration (IVDD). Here, we studied the role of the P53‐NDRG2 axis in IVDD. We found that NDRG2 was expressed in NP tissue obtained from patients with IVDD. The level of NDRG2 was positively related to the severity of IVDD, as determined by Pfirrmann grading. Subsequently, we overexpressed NDRG2 in human NP cells by adenoviral transfection and studied the effects of increased levels of NDRG2 on the viability and apoptosis of these cells. NDRG2 overexpression induced NP cell apoptosis and reduced viability in NP cells obtained from patient with IVDD. We also found that the level of P53 was elevated in NP cells from patients with IVDD and treatment with exogenous P53 upregulated NDRG2 in NP cells. Last, IVDD model was established in P53 knockout mice and the pathological changes in the intervertebral discs and NDRG2 expression were examined. P53 knockout can reduce the damage of NP tissues after IVDD surgery to some extent. Restoration of NDRG2 antagonized the effect of P53 knockout on IVDD. Collectively, this study suggests that elevated P53 in NP cells stimulates apoptosis of the cells by upregulating NDRG2 expression, thereby exacerbating IVDD.

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Genetic Alterations in Intervertebral Disc Disease

Cited by 101 publications

References 63 publications

Lumbar Disc Herniation

Lumbar Disc Herniation

Etiology and Risk Factors of Lumbar Intervertebral Disc (IVD) Degeneration

Upregulation of P53 promotes nucleus pulposus cell apoptosis in intervertebral disc degeneration through upregulating NDRG2

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