Genetic factors in intervertebral disc degeneration

Feng, Yi; Egan, Brian M.; Wang, Jinxi

doi:10.1016/j.gendis.2016.04.005

Cited by 134 publications

(146 citation statements)

References 66 publications

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“…These biological and environmental factors induce the reduction of cell number and transformation of IVD cells, resulting in decreased production of ECM of IVD owing to increased catabolic activity and decreased anabolic activities. Thereafter, the structural integrity of IVD is lost and IDD is further accelerated . One of the features of the pathomechanism of IDD in humans is increased catabolic and decreased anabolic activities, and the changes in ECM during the IDD process, characterized by the changes in the expression/structure of collagens/proteoglycans.…”

Section: Pathomechanism and Histological Features Of Human Idd And Lmentioning

confidence: 99%

“…Thereafter, the structural integrity of IVD is lost and IDD is further accelerated. 46,47 One of the features of the pathomechanism of IDD in humans is increased catabolic and decreased anabolic activities, and the changes in ECM during the IDD process, characterized by the changes in the expression/structure of collagens/proteoglycans. Owing to the difficulty in obtaining human IVD samples, especially normal human tissue, several animal models that mimic these features have been developed to elucidate the pathomechanism of IDD.…”

Section: Pathomechanism and Histological Features Of Human Idd Andmentioning

confidence: 99%

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Pathomechanism of intervertebral disc degeneration

et al. 2020

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Intervertebral disc degeneration (IDD) is the main contributor to low back pain, which is a leading cause of disability worldwide. Although substantial progress has been made in elucidating the molecular mechanisms of IDD, fundamental and long‐lasting treatments for IDD are still lacking. With increased understanding of the complex pathomechanism of IDD, alternative strategies for treating IDD can be discovered. A brief overview of the prevalence and epidemiologic risk factors of IDD is provided in this review, followed by the descriptions of anatomic, cellular, and molecular structure of the intervertebral disc as well as the molecular pathophysiology of IDD. Finally, the recent findings of intervertebral disc progenitors are reviewed and the future perspectives are discussed.

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Section: Pathomechanism and Histological Features Of Human Idd And Lmentioning

confidence: 99%

Section: Pathomechanism and Histological Features Of Human Idd Andmentioning

confidence: 99%

Pathomechanism of intervertebral disc degeneration

et al. 2020

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“…Similarly, also in humans, genetics play an important role as there have been “risk‐genes” identified in this sense. Although several predisposing genes have been reported (eg, aggrecan, collagen type I and XI, matrix metalloproteinase‐2, ‐3 and ‐9, cartilage intermediate layer protein, Interleukin‐1 and ‐6), only the association of vitamin D receptor ( VDR ) and collagen type IX ( COL9A2 ) with IVD disease has been verified in different ethnic populations . To our knowledge, no research has yet been performed on the IVD of VDR null or vitamin D‐deficient animals.…”

Section: Preclinical Animal Modelsmentioning

confidence: 99%

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

et al. 2018

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Chronic back and neck pain is a prevalent disability, often caused by degeneration of the intervertebral disc. Because current treatments for this condition are less than satisfactory, a great deal of effort is being applied to develop new solutions, including regenerative strategies. However, the path from initial promising idea to clinical use is fraught with many hurdles to overcome. Many of the keys to success are not necessarily linked to science or innovation. Successful translation to clinic will also rely on planning and awareness of the hurdles. It will be essential to plan your entire path to clinic from the outset and to do this with a multidisciplinary team. Take advice early on regulatory aspects and focus on generating the proof required to satisfy regulatory approval. Scientific demonstration and societal benefits are important, but translation cannot occur without involving commercial parties, which are instrumental to support expensive clinical trials. This will only be possible when intellectual property can be protected sufficiently to support a business model. In this manner, commercial, societal, medical, and scientific partners can work together to ultimately improve patient health. Based on literature surveys and experiences of the co‐authors, this opinion paper presents this pathway, highlights the most prominent issues and hopefully will aid in your own translational endeavors.

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“…ageing spine, the power of these studies has been poor since the sample sizes were not sufficient. The magnitude and mechanism of influence of the genetic factors on the development of IVD degeneration are still not fully understood [32]. Thus, to have a clear understanding the genetic modulation of IVD degeneration, well defined samples sharing similar environment and quantitative traits are strongly recommended [24].…”

Section: Res Med Eng Scimentioning

confidence: 99%

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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Genetic factors in intervertebral disc degeneration

Cited by 134 publications

References 66 publications

Pathomechanism of intervertebral disc degeneration

Pathomechanism of intervertebral disc degeneration

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

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

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