Genetic Association Studies in Lumbar Disc Degeneration: A Systematic Review

Eskola, Pasi J.; Lemmelä, Susanna; Kjær, Per; Solovieva, Svetlana; Männikkö, Minna; Tommerup, Niels; Lind-Thomsen, Allan; Husgafvel‐Pursiainen, Kirsti; Cheung, Kenneth M.C.; Chan, Danny; Samartzis, D; Karppinen, Jaro

doi:10.1371/journal.pone.0049995

Cited by 82 publications

(88 citation statements)

References 123 publications

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“…A systematic review carried out by Eskola et al (2012) demonstrated that the ACAN gene is among the most studied as a possible candidate for intervertebral disc degeneration, together with VDR and collagen IX (COL9A2 and COL9A3) genes. Even though the review included 52 articles, the authors concluded that the variation between study designs, populations, sampling methods, and definition of phenotypes weakened the level of evidence of the association between genetic polymorphism and disc degeneration, suggesting the need for further studies.…”

Section: Discussionmentioning

confidence: 99%

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CASE-REPORT Association between an ACAN gene variable number tandem repeat polymorphism and lumbar disc herniation: a case control study

et al. 2016

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ABSTRACT. We investigated the association between an aggrecan gene (ACAN) polymorphism and lumbar disc herniation (LDH). This was a case-control study with quinquennial age and gender groups. The study comprised 119 men and women aged between 20 and 60 from Goiânia (Brazil). Of these, 39 were allocated to the case group (Ca) and 80 to the control group (Ct). We gathered sociodemographic and clinical data, and peripheral blood samples. DNA was isolated for genotyping the ACAN variable number tandem repeat (VNTR) via conventional polymerase chain reaction (PCR). Data were statistically analyzed using the chi-square test, multiple comparison analysis, the Student t-test, and odds ratios, with a level of significance set at 5% (P ≤ 0.05). The groups were homogenous in terms of sociodemographic, anthropometric, and life style variables. The allele score for the ACAN VNTR was significantly lower in volunteers with LDH; the A22 allele was significantly more prevalent in this same group; the Ca group presented greater frequency of short alleles A13-A25, whereas the Ct group presented a higher frequency of long alleles. However, this difference was not statistically significant. In both groups, the most common alleles were A28, A27, and A29, and the A26/A26 genotype was significantly more common in the Ca group. The results showed an association between short alleles and LDH among the investigated adults (Ca), corroborating the hypothesis that aggrecan with shorter repeat lengths can lead to a reduction in the physiological proteoglycan function of intervertebral disc hydration and, consequently, increased individual susceptibility to LDH.

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Section: Discussionmentioning

confidence: 99%

“…Although it is a benign condition, it is considered a global health problem because it leads to debilitation, negative impacts on physical and work activities, decreased quality of life, and psychological distress in affected individuals (Vialle et al, 2010;Karppinen et al, 2011;Eskola et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

CASE-REPORT Association between an ACAN gene variable number tandem repeat polymorphism and lumbar disc herniation: a case control study

et al. 2016

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“…Degeneration of discs induced by biochemical and biomechanical changes traditionally attributed to age, trauma, heredity, morbid obesity, mechanical loading, and other factors impairing disc nutrition leads to low back pain (LBP). This disease is a common public socio-economic and health-care problem in western societies (Eskola et al, 2012;Phillips et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Traditional treatment methods for degenerated IVD vary, but include the conservative, involving medications, physical therapy and surgery, including discectomy and interbody fusion (Smith et al, 2011;Eskola et al, 2012). However, conservative treatment and invasive interventions are aimed at alleviating painful symptoms without preserving disc mechanics, structure and involving restoration of cellular biological function.…”

Section: Introductionmentioning

confidence: 99%

“…In particular growth factor or gene therapy is considered to be a potential method for inhibiting or reversing early intervertebral disc degeneration (IDD) (Stoyanov et al, 2011). Anabolic effects of growth factors on the ECM metabolism of IVD cells have been shown (Eskola et al, 2012). Transforming growth factor-β (TGF-β), bone morphogenetic proteins (BMPs), insulin-like growth factor-1 (IGF-1), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), growth and differentiation factor-5 (GDF-5), and others have attracted the most attention as candidates for regenerating the matrix of the IVD, restoring disc height, and reversing IDD disease (Ellman et al, 2008;Masuda, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Luo

Liu

Zhu

et al. 2016

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To construct a recombinant adenovirus vector-carrying human growth and differentiation factor-5 (GDF-5) gene, investigate the biological effects of adenovirus-mediated GDF-5 (Ad-GDF-5) on extracellular matrix (ECM) expression in human degenerative disc nucleus pulposus (NP) cells, and explore a candidate gene therapy method for intervertebral disc degeneration (IDD). Methods: Human NP cells of a degenerative disc were isolated, cultured, and infected with Ad-GDF-5 using the AdEasy-1 adenovirus vector system. On Days 3, 7, 14, and 21, the contents of the sulfated glycosaminoglycan (sGAG), deoxyribonucleic acid (DNA) and hydroxyproline (Hyp), synthesis of proteoglycan and collagen II, gene expression of collagen II and aggrecan, and NP cell proliferation were assessed. Results: The adenovirus was an effective vehicle for gene delivery with prolonged expression of GDF-5. Biochemical analysis revealed increased sGAG and Hyp contents in human NP cells infected by Ad-GDF-5 whereas there was no conspicuous change in basal medium (BM) or Ad-green fluorescent protein (GFP) groups. Only cells in the Ad-GDF-5 group promoted the production of ECM, as demonstrated by the secretion of proteoglycan and up-regulation of collagen II and aggrecan at both protein and mRNA levels. The NP cell proliferation was significantly promoted. Conclusions: The data suggest that Ad-GDF-5 gene therapy is a potential treatment for IDD, which restores the functions of degenerative intervertebral disc through enhancing the ECM production of human NP cells.

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Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

et al. 2019

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Discogenic back pain is multifactorial; hence, physicians often struggle to identify the underlying source of the pain. As a result, discogenic back pain is often hard to treat—even more so when clinical treatment strategies are of questionable efficacy. Based on a broad literature review, our aim was to define discogenic back pain into a series of more specific and interacting pathologies, and to highlight the need to develop novel approaches and treatment strategies for this challenging and unmet clinical need. Discogenic pain involves degenerative changes of the intervertebral disc, including structural defects that result in biomechanical instability and inflammation. These degenerative changes in intervertebral discs closely intersect with the peripheral and central nervous systems to cause nerve sensitization and ingrowth; eventually central sensitization results in a chronic pain condition. Existing imaging modalities are nonspecific to pain symptoms, whereas discography methods that are more specific have known comorbidities based on intervertebral disc puncture and injection. As a result, alternative noninvasive and specific diagnostic methods are needed to better diagnose and identify specific conditions and sources of pain that can be more directly treated. Currently, there are many treatments/interventions for discogenic back pain. Nevertheless, many surgical approaches for discogenic pain have limited efficacy, thus accentuating the need for the development of novel treatments. Regenerative therapies, such as biologics, cell‐based therapy, intervertebral disc repair, and gene‐based therapy, offer the most promise and have many advantages over current therapies. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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Genetic Association Studies in Lumbar Disc Degeneration: A Systematic Review

Cited by 82 publications

References 123 publications

CASE-REPORT Association between an ACAN gene variable number tandem repeat polymorphism and lumbar disc herniation: a case control study

CASE-REPORT Association between an ACAN gene variable number tandem repeat polymorphism and lumbar disc herniation: a case control study

Adenovirus-mediated GDF-5 promotes the extracellular matrix expression in degenerative nucleus pulposus cells

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

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