Vitamin D Receptor gene VDR transcripts in bone, cartilage, muscles and blood and microarray analysis of vitamin D responsive genes expression in paravertebral muscles of Juvenile and Adolescent Idiopathic Scoliosis patientsReport as inadecuate




Vitamin D Receptor gene VDR transcripts in bone, cartilage, muscles and blood and microarray analysis of vitamin D responsive genes expression in paravertebral muscles of Juvenile and Adolescent Idiopathic Scoliosis patients - Download this document for free, or read online. Document in PDF available to download.

BMC Musculoskeletal Disorders

, 13:259

First Online: 23 December 2012Received: 24 January 2012Accepted: 17 December 2012

Abstract

BackgroundVDR may be considered as a candidate gene potentially related to Idiopathic Scoliosis susceptibility and natural history. Transcriptional profile of VDR mRNA isoforms might be changed in the structural tissues of the scoliotic spine and potentially influence the expression of VDR responsive genes. The purpose of the study was to determine differences in mRNA abundance of VDR isoforms in bone, cartilage and paravertebral muscles between tissues from curve concavity and convexity, between JIS and AIS and to identify VDR responsive genes differentiating Juvenile and Adolescent Idiopathic Scoliosis in paravertebral muscles.

MethodsIn a group of 29 patients with JIS and AIS, specimens of bone, cartilage, paravertebral muscles were harvested at the both sides of the curve apex together with peripheral blood samples. Extracted total RNA served as a matrix for VDRs and VDRl mRNA quantification by QRT PCR. Subsequent microarray analysis of paravertebral muscular tissue samples was performed with HG U133A chips Affymetrix. Quantitative data were compared by a nonparametric Mann Whitney U test. Microarray results were analyzed with GeneSpring 11GX application. Matrix plot of normalized log-intensities visualized the degree of differentiation between muscular tissue transcriptomes of JIS and AIS group. Fold Change Analysis with cutoff of Fold Change ≥2 identified differentially expressed VDR responsive genes in paravertebral muscles of JIS and AIS.

ResultsNo significant differences in transcript abundance of VDR isoforms between tissues of the curve concavity and convexity were found. Statistically significant difference between JIS and AIS group in mRNA abundance of VDRl isoform was found in paravertebral muscles of curve concavity. Higher degree of muscular transcriptome differentiation between curve concavity and convexity was visualized in JIS group. In paravertebral muscles Tob2 and MED13 were selected as genes differentially expressed in JIS and AIS group.

ConclusionsIn Idiopathic Scolioses transcriptional activity and alternative splicing of VDR mRNA in osseous, cartilaginous, and paravertebral muscular tissues are tissue specific and equal on both sides of the curve. The number of mRNA copies of VDRl izoform in concave paravertebral muscles might be one of the factors differentiating JIS and AIS. In paravertebral muscles Tob2 and Med13 genes differentiate Adolescent and Juvenile type of Idiopathic Scoliosis.

KeywordsIdiopathic scoliosis Vitamin D receptor gene Spinal tissues QRT PCR analysis Paravertebral muscle microarray analysis Vitamin D responsive genes AbbreviationsAISAdolescent Idiopathic Scoliosis

BMDBone mineral density

BMPBone morphogenetic protein

Caf1Chromatin assembly factor-1

cAMPCyclic adenosine monophosphate

CDK8Cyclin dependent kinase 8

DNADeoxyribonucleic acid

ERK1ERK2: Extracellular-signal-regulated kinases 1, 2

FiFlexibility index

JISJuvenile Idiopathic Scoliosis

MAPKMitogen-activated protein kinase

MED13Mediator complex subunit 13

mRNAMessenger ribonucleic acid

QRT PCRQuantitative Real Time Reverse Transcriptase Chain Reaction

RANKLReceptor activator of nuclear factor kappa-B ligand

RAsagRotation angle relative to sagittal plane

RHiRib hump index

TGFβTransforming growth factor beta

Tob2Transducer of erB-2

VDRVitamin D receptor

VDRlVitamin D receptor long isoform

VDRsVitamin D receptor short isoform.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2474-13-259 contains supplementary material, which is available to authorized users.

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Author: Roman Nowak - Justyna Szota - Urszula Mazurek

Source: https://link.springer.com/







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