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

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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.

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Adolescent idiopathic scoliosis: a new classification to determine extent of spinal arthrodesis.

L G Lenke, R Betz, J. Harms … (2001)

The lack of a reliable, universally acceptable system for classification of adolescent idiopathic scoliosis has made comparisons between various types of operative treatment an impossible task. Furthermore, long-term outcomes cannot be determined because of the great variations in the description of study groups. We developed a new classification system with three components: curve type (1 through 6), a lumbar spine modifier (A, B, or C), and a sagittal thoracic modifier (-, N, or +). The six curve types have specific characteristics, on coronal and sagittal radiographs, that differentiate structural and nonstructural curves in the proximal thoracic, main thoracic, and thoracolumbar/lumbar regions. The lumbar spine modifier is based on the relationship of the center sacral vertical line to the apex of the lumbar curve, and the sagittal thoracic modifier is based on the sagittal curve measurement from the fifth to the twelfth thoracic level. A minus sign represents a curve of less than +10 degrees, N represents a curve of 10 degrees to 40 degrees, and a plus sign represents a curve of more than +40 degrees. Five surgeons, members of the Scoliosis Research Society who had developed the new system and who had previously tested the reliability of the King classification on radiographs of twenty-seven patients, measured the same radiographs (standing coronal and lateral as well as supine side-bending views) to test the reliability of the new classification. A randomly chosen independent group of seven surgeons, also members of the Scoliosis Research Society, tested the reliability and validity of the classification as well. The interobserver and intraobserver kappa values for the curve type were, respectively, 0.92 and 0.83 for the five developers of the system and 0.740 and 0.893 for the independent group of seven scoliosis surgeons. In the independent group, the mean interobserver and intraobserver kappa values were 0.800 and 0.840 for the lumbar modifier and 0.938 and 0.970 for the sagittal thoracic modifier. These kappa values were all in the good-to-excellent range (>0.75), except for the interobserver reliability of the independent group for the curve type (kappa = 0.74), which fell just below this level. This new two-dimensional classification of adolescent idiopathic scoliosis, as tested by two groups of surgeons, was shown to be much more reliable than the King system. Additional studies are necessary to determine the versatility, reliability, and accuracy of the classification for defining the vertebrae to be included in an arthrodesis.

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Smad2 and 3 transcription factors control muscle mass in adulthood.

Roberta Sartori, Giulia Milan, Maria Patron … (2009)

Loss of muscle mass occurs in a variety of diseases, including cancer, chronic heart failure, aquired immunodeficiency syndrome, diabetes, and renal failure, often aggravating pathological progression. Preventing muscle wasting by promoting muscle growth has been proposed as a possible therapeutic approach. Myostatin is an important negative modulator of muscle growth during myogenesis, and myostatin inhibitors are attractive drug targets. However, the role of the myostatin pathway in adulthood and the transcription factors involved in the signaling are unclear. Moreover, recent results confirm that other transforming growth factor-beta (TGF-beta) members control muscle mass. Using genetic tools, we perturbed this pathway in adult myofibers, in vivo, to characterize the downstream targets and their ability to control muscle mass. Smad2 and Smad3 are the transcription factors downstream of myostatin/TGF-beta and induce an atrophy program that is muscle RING-finger protein 1 (MuRF1) independent. Furthermore, Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but partially dependent of mammalian target of rapamycin (mTOR) signaling. Thus myostatin and Akt pathways cross-talk at different levels. These findings point to myostatin inhibitors as good drugs to promote muscle growth during rehabilitation, especially when they are combined with IGF-1-Akt activators.

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Health and function of patients with untreated idiopathic scoliosis: a 50-year natural history study.

Ignacio Ponseti, Kevin Spratt, Michael Peterson … (2003)

Previous long-term studies of idiopathic scoliosis have included patients with other etiologies, leading to the erroneous conclusion that all types of idiopathic scoliosis inevitably end in disability. Late-onset idiopathic scoliosis (LIS) is a distinct entity with a unique natural history. To present the outcomes related to health and function in untreated patients with LIS. Prospective natural history study performed at a midwestern university with outpatient evaluation of patients who presented between 1932 and 1948. At 50-year follow-up, which began in 1992, 117 untreated patients were compared with 62 age- and sex-matched volunteers. The patients' mean age was 66 years (range, 54-80 years). Mortality, back pain, pulmonary symptoms, general function, depression, and body image. The estimated probability of survival was approximately 0.55 (95% confidence interval [CI], 0.47-0.63) compared with 0.57 expected for the general population. There was no significant difference in the demographic characteristics of the 2 groups. Twenty-two (22%) of 98 patients complained of shortness of breath during everyday activities compared with 8 (15%) of 53 controls. An increased risk of shortness of breath was also associated with the combination of a Cobb angle greater than 80 degrees and a thoracic apex (adjusted odds ratio, 9.75; 95% CI, 1.15-82.98). Sixty-six (61%) of 109 patients reported chronic back pain compared with 22 (35%) of 62 controls (P =.003). However, of those with pain, 48 (68%) of 71 patients and 12 (71%) of 17 controls reported only little or moderate back pain. Untreated adults with LIS are productive and functional at a high level at 50-year follow-up. Untreated LIS causes little physical impairment other than back pain and cosmetic concerns.

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Author and article information

Journal

Journal ID (nlm-ta): BMC Musculoskelet Disord

Journal ID (iso-abbrev): BMC Musculoskelet Disord

Title: BMC Musculoskeletal Disorders

Publisher: BioMed Central

ISSN (Electronic): 1471-2474

Publication date Collection: 2012

Publication date (Electronic): 23 December 2012

Volume: 13

Page: 259

Affiliations

[1 ]Orthopaedics Clinic Medical University of Silesia, Wojewódzki Szpital Specjalistyczny nr5 41-200 Sosnowiec, Pl. Medyków 1, Poland

[2 ]Department of Molecular Biology Medical University of Silesia, 41-100 Sosnowiec, ul.Narcyzów 1, Poland

Article

Publisher ID: 1471-2474-13-259

DOI: 10.1186/1471-2474-13-259

PMC ID: 3532837

PubMed ID: 23259508

SO-VID: fb618eb8-982f-4dcb-94cb-4734028dd879

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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

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Most cited references 58

Adolescent idiopathic scoliosis: a new classification to determine extent of spinal arthrodesis.

Smad2 and 3 transcription factors control muscle mass in adulthood.

Health and function of patients with untreated idiopathic scoliosis: a 50-year natural history study.

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