The Evaluation of Proteoglycan Levels and the Possible Role of <i>ACAN</i> Gene (c.6423T&gt;C) Variant in Patients with Lumbar Disc Degeneration Disease

Yaltırık, Cumhur Kaan; Timirci-Kahraman, Özlem; Gulec-Yilmaz, Seda; Özdoğan, Selçuk; Atalay, Başar; İsbır, Turgay

doi:10.21873/invivo.11488

Cited by 11 publications

(10 citation statements)

References 42 publications

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“…The aggrecan gene (ACAN) is a member of the aggrecan and versican proteoglycan family that encodes a major proteoglycan component of the hyaline cartilage and the nucleus pulposus (NP) in the form of chondroitin sulfate and keratan sulfate chains, respectively [22,23]. It is directly responsible for maintaining disc hydration, propagated by the covalent bonding of anionic glycosaminoglycans, and thus the loadbearing and shock-absorbing functions of the IVD [9,22]. Hence, the loss of ACAN gene function, resulting in disc dehydration, has been identified as an early indicator of disc degeneration and a potentiator of NP herniation [22,24].…”

Section: Aggrecanmentioning

confidence: 99%

“…It is directly responsible for maintaining disc hydration, propagated by the covalent bonding of anionic glycosaminoglycans, and thus the loadbearing and shock-absorbing functions of the IVD [9,22]. Hence, the loss of ACAN gene function, resulting in disc dehydration, has been identified as an early indicator of disc degeneration and a potentiator of NP herniation [22,24]. The ACAN gene consists of two domains, CS1 and CS2, where a VNTR polymorphism in the CS1 gene domain, located in exon 12, has proven to result in variant ACAN structures propagating the loss of function and ultimate IVDD [5].…”

Section: Aggrecanmentioning

confidence: 99%

“…The ACAN gene consists of two domains, CS1 and CS2, where a VNTR polymorphism in the CS1 gene domain, located in exon 12, has proven to result in variant ACAN structures propagating the loss of function and ultimate IVDD [5]. [22]. These inconsistent findings can be attributed to unknown interactions between other associated genes and the differences found within the distribution of alleles between ethnic groups [10].…”

Section: Aggrecanmentioning

confidence: 99%

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Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two

Covarrubias¹,

Jarrah²

2021

Cureus

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Intervertebral disc (IVD) degeneration is a progressive and painful pathology that can root from mechanical, biochemical, and environmental stressors. However, recent advancements in biogenetics have now found a predominating genetic influence. Nevertheless, despite these advancements, the pathophysiology of IVD degeneration remains poorly understood. In the first of our two-part series, we will characterize some of the most recent and best-studied genes in the context of intervertebral disc degeneration. We will attempt to formulate the first contemporary gene guide that characterizes the genetic profile of IVD degeneration. The genes of interest include aggrecan (ACAN), matrix metalloproteinase 2 (MMP2), vitamin D receptor (VDR), interleukin 1 alpha (IL1A), and those encoded for collagens such as collagen type XI alpha 1 chain (COL11A1), collagen type I alpha 1 chain (COL1A1), collagen type IX alpha 2 chain (COL9A2), and collagen type IX alpha 3 chain (COL9A3). Genetic analysis studies reveal that these genes play vital roles in maintaining the structural integrity of the intervertebral disc, activating enzymes involved in the extracellular matrix, and promoting connective tissue formation. Nevertheless, characterizing these genes alone is not enough to understand the pathophysiology of IVD degeneration. Therefore, further studies are warranted to understand molecular signalling pathways of IVD degeneration better and ultimately create more sophisticated genetic and cell-based therapies to improve patient outcomes.

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Section: Aggrecanmentioning

confidence: 99%

Section: Aggrecanmentioning

confidence: 99%

Section: Aggrecanmentioning

confidence: 99%

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Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two

Covarrubias¹,

Jarrah²

2021

Cureus

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“…In the past decade, multiple studies on gene expression profiling worked on autophagy and LDD, with piles of candidate genes identified [ 8 , 9 ]. The purpose of our research was to find candidate genes and signaling pathways in relationship with autophagy and LDD by using a bioinformatics approach and to discover drugs that target LDD- and autophagy-related genes.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of lumbar disc degeneration and autophagy-related candidate genes, pathways, and targeting drugs

Zhao

2021

J Orthop Surg Res

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Background Lumbar disc degeneration (LDD) is an essential pathological mechanism related to low back pain. Current research on spinal surgery focused on the sophisticated mechanisms involved in LDD, and autophagy was regarded as an essential factor in the pathogenesis. Objectives Our research aimed to apply a bioinformatics approach to select some candidate genes and signaling pathways in relationship with autophagy and LDD and to figure out potential agents targeting autophagy- and LDD-related genes. Materials and methods Text mining was used to find autophagy- and LDD-related genes. The DAVID program was applied in Gene Ontology and pathway analysis after selecting these genes. Several important gene modules were obtained by establishing a network of protein-protein interaction and a functional enrichment analysis. Finally, the selected genes were searched in the drug database to find the agents that target LDD- and autophagy-related genes. Results There were 72 genes related to “autophagy” and “LDD.” Three significant gene modules (22 genes) were selected by using gene enrichment analysis, which represented 4 signaling pathways targeted by 32 kinds of drugs approved by the Food and Drug Administration (FDA). The interactions between drugs and the genes were also identified. Conclusion To conclude, a method was proposed in our research to find candidate genes, pathways, and drugs which were involved in autophagy and LDD. We discovered 22 genes, 4 pathways, and 32 potential agents, which provided a theoretical basis and new direction for clinical and basic research on LDD.

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“…Many gene expression pro ling studies have focused on LDD and autophagy in the last decade, and hundreds of candidate genes have been identi ed [8,9]. These genes have different functions and are involved in a variety of processes, including biological processes (BP), cellular components (CC), molecular function (MF), signal pathways and protein-protein interaction (PPI) networks.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of lumbar disc degeneration and autophagy-related candidate genes, pathways, and targeting Drugs

Zhao

2020

Preprint

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Background Lumbar disc degeneration (LDD) is a major pathological process implicated in low back pain. At present, the research in the fields of spinal surgery has highlighted the complex mechanisms underlying LDD, with autophagy being considered as one of the important processes involved. Objectives We aimed to identify the genes and molecular pathways associated with LDD and autophagy using computational tools and publicly available data, and to identify drugs targeting the relevant genes associated with LDD and autophagy. Materials and Methods We used text mining to detect the LDD and autophagy-associated genes, and the intersection of the two gene sets was selected for gene ontology analysis using the DAVID program. We then constructed protein–protein interaction networks, followed by a functional enrichment analysis, from which we obtained three significant gene modules. Finally, the final list of genes was queried against the Drug Gene Interaction database to find drug candidates targeting relevant genes associated with LDD and autophagy. Results Our analysis identified 72 genes common to both the “LDD” and “Autophagy” text mining concepts. Gene enrichment analysis yielded three significant gene modules (22 genes), which represent four significant pathways and could be targeted by 32 Food and Drug Administration (FDA)-approved drug molecules, and identified the drug–gene interactions. Conclusion Using text mining, pathway analysis tools, and drug–gene interaction analysis for gene screening, signal pathway analysis and drug discovery can provide new ideas for the scientific research and clinical treatment.

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The Evaluation of Proteoglycan Levels and the Possible Role of ACAN Gene (c.6423T>C) Variant in Patients with Lumbar Disc Degeneration Disease

Cited by 11 publications

References 42 publications

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two

Comprehensive analysis of lumbar disc degeneration and autophagy-related candidate genes, pathways, and targeting drugs

Comprehensive analysis of lumbar disc degeneration and autophagy-related candidate genes, pathways, and targeting Drugs

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