Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc

Sivan, Uri; Hayes, Anthony Joseph; Wachtel, Ellen; Caterson, Bruce; Merkher, Yulia; Maroudas, Alice; Brown, Sharon J.; Roberts, Sally

doi:10.1007/s00586-013-2767-8

Cited by 102 publications

(84 citation statements)

References 104 publications

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“…Spontaneous disc regression is currently believed to be a consequence of macrophage activity. [35,36] type XI [37] all over, mostly NP regulates fibril diameter (smaller if this collagen is more abundant) influencing mechanical properties [35,38] beaded-filament forming collagens type VI all over, mostly NP helps cell fixation to the matrix and facilitates collagen bundles' sliding and lubrication [39,40] FACIT collagens type IX NP maintains matrix integrity [41,42] type XII AF might regulate fibrillogenesis [29,43] [66,[74][75][76]. However, when an imbalance occurs, degradation products might trigger inflammation.…”

Section: The Origin Of Inflammation In Intervertebral Discmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

335

256

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Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.

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Section: The Origin Of Inflammation In Intervertebral Discmentioning

confidence: 99%

Inflammation in intervertebral disc degeneration and regeneration

Molinos

Almeida

Caldeira

et al. 2015

J. R. Soc. Interface.

335

256

View full text Add to dashboard Cite

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“…We hypothesize that this increase in FCD represents an accumulation of fragmented GAG chains that have been cleaved and expunged from the NP. These fragmented GAG chains may become entangled in the dense and charged CEP environment before slowly leaving the disc altogether (Sivan et al, 2013; Sivan et al, 2006). This observation is qualitatively supported by increased proteoglycan staining in CEP.…”

Section: Discussionmentioning

confidence: 99%

Human cartilage endplate permeability varies with degeneration and intervertebral disc site

DeLucca

Cortés

Jacobs

et al. 2016

Journal of Biomechanics

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Despite the critical functions the human cartilage endplate (CEP) plays in the intervertebral disc, little is known about its structural and mechanical properties and their changes with degeneration. Quantifying these changes with degeneration is important for understanding how the CEP contributes to the function and pathology of the disc. Therefore the objectives of this study were to quantify the effect of disc degeneration on human CEP mechanical properties, determine the influence of superior and inferior disc site on mechanics and composition, and simulate the role of collagen fibers in CEP and disc mechanics using a validated finite element model. Confined compression data and biochemical composition data were used in a biphasic-swelling model to calculate compressive extrafibrillar elastic and permeability properties. Tensile properties were obtained by applying published tensile test data to an ellipsoidal fiber distribution. Results showed that with degeneration CEP permeability decreased 50–60% suggesting that transport is inhibited in the degenerate disc. CEP fibers are organized parallel to the vertebrae and nucleus pulposus and may contribute to large shear strains (0.1–0.2) and delamination failure of the CEP commonly seen in herniated disc tissue. Fiber-reinforcement also reduces CEP axial strains thereby enhancing fluid flux by a factor of 1.8. Collectively, these results suggest that the structure and mechanics of the CEP may play critical roles in the solute transport and disc mechanics.

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“…Aggrecan is a large aggregating proteoglycan and a main structural component of the intervertebral disc and vertebral end plate [49]. Any factor that alter the synthesis and function of the aggrecan in the extracellular matrix would make the disc vulnerable to biomechanical forces leading to increased secretion of catabolic enzymes and subsequent degeneration [50].…”

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes

et al. 2017

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IntroductionLumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes.ObjectivesThe study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed.MethodsA descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster.ResultsMean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool.ConclusionsSNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent.

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Biochemical composition and turnover of the extracellular matrix of the normal and degenerate intervertebral disc

Cited by 102 publications

References 104 publications

Inflammation in intervertebral disc degeneration and regeneration

Inflammation in intervertebral disc degeneration and regeneration

Human cartilage endplate permeability varies with degeneration and intervertebral disc site

Single Nucleotide Variants of Candidate Genes in Aggrecan Metabolic Pathway Are Associated with Lumbar Disc Degeneration and Modic Changes

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