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

abstract: ...Background VDR 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. Methods In 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. Results No 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. Conclusions In 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.

... 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. Conclusions In 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. Idiopathic scoliosis Vitamin D receptor gene Spinal tissues QRT PCR analysis Paravertebral muscle microarray analysis Vitamin D responsive genes Background Idiopathic scoliosis is the most common spinal deformity observed in humans. It is characterized by three dimensional changes of spinal shape observed as lateral curvature in frontal, thoracic lordosis in sagittal and axial

... splicing of VDR exons. This study reports on VDR expression at the mRNA level in spinal tissues of the idiopathic scoliosis patients with different age of deformity onset pointing at differences in VDRl isoform transcript abundance and indicating Tob2 and Med13 as genes differentially expressed in paravertebral muscles of the curve concavity of Juvenile and Adolescent Idiopathic Scoliosis. The main aims of the study were: Determination of differences in transcript abundance of VDR isoforms in osseous

... and Adolescent Idiopathic Scoliosis in paravertebral muscular tissue samples. The cut off was set at Fold Change 2. The results of the analysis are presented as scatter plots, (Figure 6 ). In the muscular tissue samples harvested form curve concavity only two out of the 75 VDRs responsive genes appeared to be differentially expressed in group A-JIS and B-AIS: Tob2 and MED13. Both genes were up regulated in the population of group B- Adolescent Idiopathic Scoliosis. Tob2 gene was also

... group in muscular tissue samples from both sides of the curve. Fold change analysis of the results permitted to identify Tob2 and MED13 as VDR responsive genes differentially expressed in Juvenile and Adolescent Scoliosis group in muscular tissue samples of curve concavity. Both genes were up regulated in Adolescent Scoliosis group. Interestingly Tob2 was also differentially expressed at the curve convexity but appeared to be up regulated in Juvenile Idiopathic Scoliosis. Tob2 is one of the members

... expressed throughout skeletal muscle development and contributed to phenotypic differences in muscle in experimental animals [ 66 ]. Tob can associate with the Smads transcription complex and affect Smad-mediated gene expression [ 67 ]. Phosphorylation of Tob1 by ERK1 and ERK2 negatively regulates the antiprolipherative activity of Tob1 [ 65 ]. Both Tob1 and Tob2 also interact with human Caf1 and form transcriptional complexes that activate or suppress target gene transcription [ 65 ]. Tob genes play also important role in bone formation and resorption. Tob1 controls bone formation by suppressing BMP signaling and by inhibiting sex hormone signaling in osteoblastic cells [ 65 ]. Tob2 decreases osteoclasts differentiation and regulates RANKL expression in stromal cells. Probably in regulating RANKL expression Tob2 interacts with VDR [ 67 ]. It seems that Tob1 and Tob2 may interfere in bone formation as Tob1 deficient mice present with osteopetrotic phenotype while Tob2 deficient animals are

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Gene: TOB2 - transducer of ERBB2, 2 - (NCBI)

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