Pathophysiology of Degenerative Disc Disease

Kim, Choong-Young

doi:10.4184/asj.2009.3.1.39

Cited by 127 publications

(116 citation statements)

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“…The intervertebral disc consists of three morphologically distinct regions, which are the nucleus pulposus (NP), annulus fibrosis and cartilaginous endplates (7). The central NP is a gelatinous matrix that is composed of large aggregating proteoglycans and a loose network of collagen.…”

Section: Introductionmentioning

confidence: 99%

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Xue

Liu

et al. 2015

International Journal of Molecular Medicine

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Abstract. The present study aimed to explore potential molecular targets and gain further insights into the mechanism of intervertebral disc degeneration (IDD) progression. Microarray datasets of GSE19943, GSE15227 and GSE34095 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) in 3 IDD specimens compared with 3 controls in GSE34095, DEGs in 7 grade III and 3 grade IV samples compared with 5 grade II samples in GSE19943, and differentially expressed miRNAs in 3 degenerated samples compared with 3 controls in GSE15227 were screened. Grade III-and IV-specific networks were constructed and grade-specific genes were extracted. The network features were analyzed, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis of grade-specific genes and DEGs identified in GSE34095. Furthermore, miRNA-pathway interactions were analyzed using Fisher's exact test. Tumor protein p53 (TP53) was a hub gene in the grade III-specific network and ubiquitin C (UBC) was identified to be a hub gene in the grade IV-specific network. Six significant features were identified by grade-specific network topology analysis. Grade-specific genes and DEGs were involved in different GO terms and pathways. Differentially expressed miRNAs were identified to participate in 35 pathways, among which 6 pathways were significantly enriched by DEGs, including apoptosis. The present study identified that key genes (TP53 and UBC) and miR-129-5p may participate in the mechanism of IDD progression. Thus, they may be potential therapeutic targets for IDD.

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Section: Introductionmentioning

confidence: 99%

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Xue

Liu

et al. 2015

International Journal of Molecular Medicine

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“…Progressive and serious changes also occur with increasing age. [3,4] The most common cause of low back or upper neck pain problems are degenerations that occur in the IV discs. The causes of these degenerations are fluid loss in nucleus pulposus, rupture of annulus fibrosus, weakening of the connections between the intervertebral foramen and loss of function.…”

Section: Introductionmentioning

confidence: 99%

Intervertebral disc heights and concavity index of the lumbar spine in young healthy adults

Demır¹,

Atay²,

Seringec³

et al. 2018

Anatomy

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Objectives: The aim of this study was to investigate lumbar intervertebral disc heights and concavity index of the lumbar spine, and the influence of age, gender, weight, height and body mass index (BMI) on these parameters. Methods:The study was conducted on 150 health young subjects (age 18 to 27) without any disorder which affects the lumbar spine and the discs. Subjects underwent standard standing lateral lumbar radiography. Mann-Whitney U test and Spearman's correlation test were used for statistical analysis.Results: Of the 150 subjects (age range, 18-27 years), 80 (53.3%) were women and 70 (46.7%) were men. Men presented higher lumbar disc values than women. In both genders, disc height increased from T12-L1 to L4-L5, and then decreased at L5-S1. The heights of all lumbar discs increased with age, weight, height and BMI in both genders. Women demonstrated a higher concavity index at L2, L3 and L4 vertebrae compared to men, whereas men showed a higher concavity index value at L5 vertebra. The concavity index of T12, L1, L2, L3 and L4 vertebrae decreased with age. Conclusion:Our results will serve as guidelines and references for further studies, radiologists and spinal surgeons.

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“…synovitis followed by articular cartilage disruption, capsular laxity and joint subluxation. There is formation of hypertrophic osteophytes at the margins of the facet joints and periarticular fibrosis resulting in stiffness [65]. The ligamentum flavum buckles and facet joint overrides.…”

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confidence: 99%

“…Complex loading in bending and compression can lead to radial fissures and disc prolapse either in a single loading cycle or by fatigue failure [62][63][64]. Axial rotation probably enhances the vulnerability of the posterior region of the IVD to damage and reduces the load required to cause disc failure [65]. …”

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confidence: 99%

“…Also there is abundant mast cells in the granulation tissue zones. These mast cells contribute to disc tissue inflammation, neovascularization, fibrosis formation, disc tissue degradation and secrete the nerve growth factor which may be a signaling substance such as TNF-α and IL-1 and play a role in the development of back pain [65].Recent evidence suggest that the sensory nerve supply of the disc is similar to that of certain enteric structures and represents a form of visceral pain [76]. It is confirmed that a large proportion of nociceptive nerve fibres arising from the annulus of the lower lumbar discs pass through the sympathetic trunks in a non-segmental manner.…”

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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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Pathophysiology of Degenerative Disc Disease

Cited by 127 publications

References 42 publications

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Identification of the potential molecular targets for human intervertebral disc degeneration based on bioinformatic methods

Intervertebral disc heights and concavity index of the lumbar spine in young healthy adults

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

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