Asymmetric expression of melatonin receptor mRNA in bilateral paravertebral muscles in adolescent idiopathic scoliosis.
ABSTRACT Comparison of melatonin receptor mRNA expression in bilateral paravertebral muscles in adolescent idiopathic scoliosis (AIS). OBJECTIVES.: To investigate the change of melatonin receptor mRNA expression in bilateral paravertebral muscles in AIS, congenital scoliosis (CS), and control in order to analyze its association to the pathogenesis of AIS.
Muscle imbalance and asymmetry of stretch receptors in the paravertebral muscles of patients with AIS were supposed to have a large role to play in the development and production of the deformity. Melatonin is a focus of studies of the mechanism underlying the development of scoliosis, and there is no research on the expression of melatonin receptors in the paravertebral muscles of patients with AIS.
Twenty cases with average age of 15.1 +/- 2.2 years and average Cobb angle of 56.2 degrees +/- 16.1 degrees, including 10 cases with Cobb angle >50 degrees and 10 cases with Cobb angle < or =50 degrees, were included in AIS group. The apical vertebrae were from T6 to T11. Twelve cases with an average age of 11.6 +/- 3.2 years and average Cobb angle of 59.2 degrees +/- 33.3 degrees were included in CS group. The apical vertebrae were from T7 to T12. Ten cases without scoliosis were in the control group. The mRNA expression of melatonin receptor subtype MT1 and MT2 was detected by the RT-PCR method.
The MT2 mRNA expression on the concave side of the paravertebral muscle was higher than that on the convex side in AIS and CS groups (P < 0.05), but the MT1 mRNA expression showed no significant difference (P > 0.05). In the AIS group, the ratio of MT2 mRNA expression on the concave side compared with the convex side in cases with Cobb angle >50 degrees and cases with Cobb angle < or =50 degrees showed no significant difference (P > 0.05). The MT1 and MT2 mRNA expression showed no significant difference in control group (P > 0.05).
The melatonin receptor expression in bilateral paravertebral muscles in AIS is asymmetric, which may be a secondary change. The bilateral asymmetry in force exerted on the scoliotic spine may be the cause.
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ABSTRACT: To evaluate the effectiveness and to identify the predictive factors of standardized brace treatment for girls with adolescent idiopathic scoliosis (AIS). From July 2003 to July 2009, 142 girls with AIS completed standardized brace treatment. These patients had a mean age of (13.1 ± 1.5) years (range, 10.1-15.9 years), a mean main curve of 29.6°± 5.4° (range, 20°-40°), and a mean Risser grade of 2.0 ± 1.5 (range, 0-4) before brace treatment. Based on whether their scoliosis progressed or not, patients were divided into two groups: progressed (Group Pr, n = 27, 19%) and non-progressed (Group NP, n = 115, 81%), and were then divided into a further two groups: surgery (Group Su, n = 18, 13%) and non-surgery (Group NS, n = 124, 87%). χ(2) and logistic regression analyses were performed to investigate factors predicting outcomes of brace treatment. The duration of brace treatment in all patients averaged 2.5 ± 1.0 years (range, 0.6-5.9). χ(2) analysis revealed that patients with progressive curves tended to be younger, with lower Risser grade, initial larger curve magnitude and a main thoracic curve pattern. Using stepwise logistic regression, pre-menarche status (P= 0.00028) and a main thoracic curve pattern (P= 0.012) were found to be independent risk factors of curve progression despite brace treatment, while an initial Cobb angle >30° (P= 0.022) was an additional independent risk factor of curve requiring surgery due to progression. Brace treatment can prevent curve progression in most girls with AIS. The outcomes of brace treatment in these girls are influenced by growth status, curve pattern and curve magnitude. Less mature patients, and those with larger curves and thoracic curves are at risk of scoliosis progression despite brace treatment.Orthopaedic Surgery 11/2010; 2(4):285-90.
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ABSTRACT: Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity in children. Studies have shown low melatonin levels resulting from pinealectomy in chickens and mice result in the development scoliosis, whereas supplementation with melatonin after the pinealectomy prevented it. The mere characterization of low melatonin levels is not sufficient to explain the development of idiopathic scoliosis in primates and humans, but we hypothesize that a mutation in melatonin-related receptors may be involved with the development of scoliosis. The coding, splice-site, and promoter regions of 3 melatonin-related receptors (hMel-1B, RORalpha, and GPR50) were evaluated by DNA sequencing for variants associated with the phenotype of adolescent idiopathic scoliosis. An initial screening of 50 scoliosis patients with adolescent idiopathic scoliosis was compared with 50 controls by DNA sequencing of the 3 receptors. Additional cases and controls were evaluated when genetic variants were observed (for a total of 885 individuals). No significant differences were found in the hMel-1B and RORalpha receptors. We found 2 cSNPs in GPR50 (rs561077 and rs13440581) in the initial 50 patients. To evaluate the significance of these cSNPs, an additional 356 patients and 429 controls were analyzed. When the combined groups were analyzed, no significant associations were observed. Despite the observed relationship between melatonin and scoliosis, there is no significant association between mutations found in any known melatonin-related receptors with adolescent idiopathic scoliosis. The strong evidence of a melatonin-related cause for the development of idiopathic scoliosis still encourages research into undiscovered melatonin-related receptors, melatonin-related hormones, and the catalytic enzymes for the serotonin-melatonin pathway. This investigation is a genetic testing of the remaining currently known melatonin-related receptors that have not been analyzed earlier for association with AIS. Given the support in the literature of a relationship between melatonin and AIS, we have shown no mutations in any of the known melatonin-related receptor in patients with AIS.Journal of pediatric orthopedics 09/2010; 30(6):539-43. · 1.23 Impact Factor
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ABSTRACT: Melatonin has a number of beneficial metabolic actions and reduced levels of melatonin may contribute to type 2 diabetes. The present study investigated the metabolic pathways involved in the effects of melatonin on mitochondrial function and insulin resistance in rat skeletal muscle. The effect of melatonin was tested both in vitro in isolated rats skeletal muscle cells and in vivo using pinealectomized rats (PNX). Insulin resistance was induced in vitro by treating primary rat skeletal muscle cells with palmitic acid for 24h. Insulin-stimulated glucose uptake was reduced by palmitic acid followed by decreased phosphorylation of AKT which was prevented my melatonin. Palmitic acid reduced mitochondrial respiration, genes involved in mitochondrial biogenesis and the levels of tricarboxylic acid cycle intermediates whereas melatonin counteracted all these parameters in insulin-resistant cells. Melatonin treatment increases CAMKII and p-CREB but had no effect on p-AMPK. Silencing of CREB protein by siRNA reduced mitochondrial respiration mimicking the effect of palmitic acid and prevented melatonin-induced increase in p-AKT in palmitic acid-treated cells. PNX rats exhibited mild glucose intolerance, decreased energy expenditure and decreased p-AKT, mitochondrial respiration, p-CREB and PGC-1alpha levels in skeletal muscle which were restored by melatonin treatment in PNX rats. In summary, we showed that melatonin could prevent mitochondrial dysfunction and insulin resistance via activation of CREB-PGC-1 alpha pathway. Thus, the present work shows that melatonin play an important role in skeletal muscle mitochondrial function which could explain some of the beneficial effects of melatonin in insulin resistance states. This article is protected by copyright. All rights reserved.Journal of Pineal Research 07/2014; · 7.30 Impact Factor