Genetic polymorphisms associated with intervertebral disc degeneration

Mayer, Johannes; Iatridis, James C.; Chan, Danny; Qureshi, Sheeraz A.; Gottesman, Omri; Hecht, Andrew C.

doi:10.1016/j.spinee.2013.01.041

Cited by 176 publications

(188 citation statements)

References 163 publications

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“…Collagen IX is thought to play an important role in connecting various types of collagens together, particularly collagen type II. Various studies found SNPs located on either COL9A2 or COL9A3 which may be associated with increased risk of DDD [27]. Trp3, a common SNP in COL9A3 has strong association for IVD degeneration [28].…”

Section: Genetic Influence On Ivd Degenerationmentioning

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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Section: Genetic Influence On Ivd Degenerationmentioning

confidence: 99%

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

Debnath¹

2018

RMES

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“…(189) Moreover, the recombinant human GDF-5 (rhGDF-5) enhances cell proliferation and matrix synthesis and accumulation by both bovine NP and AF cells. (190) Some epidemiologic studies highlighted that DD may be caused to a large degree by hereditary factors with apparently a relatively minor effects of environmental and behavioral risk factors (191)(192)(193)(194)(195), which indicated that genetic factors might play an important role in the pathogenesis of IDD.…”

Section: Lbp Pathophysiologymentioning

confidence: 99%

“…(197) The problem of immune rejection is likely to be even less for allogenic MSCs, since MSCs are capable of escaping alloantigen recognition. (194,197) Adipose-tissue-derived stromal cell (ADSC) show potential for restoring degenerative discs and may prove effective in the treatment of IVD. The results of ADSC implantation studies in a DD model were promising, indicating that ADSCs could maintain their viability and proliferate within the rat IVD.…”

Section: Lbp Pathophysiologymentioning

confidence: 99%

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Intervertebral Disc Degeneration and Low Back Pain: Molecular Mechanisms and Stem Cell Therapy

2018

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BACKGROUND: Low back pain (LBP) mostly caused by disc degeneration, reflects to a tremendous of health care system and economy. More knowledge about these underlying pathologies will improve the opportunities that may represent critical therapeutic targets.CONTeNT: Basic research is advancing the understanding of the pathogenesis and management of LBP at the molecular and genetic levels. Cytokines such as matrix metalloproteinases, phospholipase A2, nitric oxide, and tumor necrosis factor-α are thought to contribute to the development of LBP. Mesenchymal stem cells (MSCs) transplant to cartilage-like cells and secrete extracellular matrix and encourage nucleus pulposus (NP) cell activity Abstract R E V I E W A R T I C L Einhibiting NP cell apoptosis, together with some chemical mediators such as cytokines and growth factors become a safe and effective new strategy for intervertebral disc degeneration (IDD) treatment and regeneration.SUMMARy: IDD occurs where there is a loss of homeostatic balance with a predominantly catabolic metabolic profile. A basic understanding of the molecular changes occurring in the degenerating disc is important for practicing clinicians to help them to inform patients to alter lifestyle choices, identify beneficial or harmful supplements, or offer new biologic, genetic, or stem cell therapies.

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“…The SNP in the VDR gene can cause alteration in the structure of the VDR protein [6]. Moreover, some variation is strongly associated with different abilities of the VDR protein to bind Transcription Factor II B (TFIIB), leading to divergent gene transcription coupled with VDR [7].…”

Section: Introductionmentioning

confidence: 99%