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首页> 外文期刊>International Journal of Medical Sciences >A New Look at Causal Factors of Idiopathic Scoliosis: Altered Expression of Genes Controlling Chondroitin Sulfate Sulfation and Corresponding Changes in Protein Synthesis in Vertebral Body Growth Plates
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A New Look at Causal Factors of Idiopathic Scoliosis: Altered Expression of Genes Controlling Chondroitin Sulfate Sulfation and Corresponding Changes in Protein Synthesis in Vertebral Body Growth Plates

机译：特发性脊柱侧弯的病因新视角：控制硫酸软骨素硫酸化基因的表达改变及椎体生长板中蛋白质合成的相应变化

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Background: In a previous report, we demonstrated the presence of cells with a neural/glial phenotype on the concave side of the vertebral body growth plate in Idiopathic Scoliosis (IS) and proposed this phenotype alteration as the main etiological factor of IS. In the present study, we utilized the same specimens of vertebral body growth plates removed during surgery for Grade III-IV IS to analyse gene expression. We suggested that phenotype changes observed on the concave side of the vertebral body growth plate can be associated with altered expression of particular genes, which in turn compromise mechanical properties of the concave side. Methods: We used a Real-Time SYBR Green PCR assay to investigate gene expression in vertebral body growth plates removed during surgery for Grade III-IV IS; cartilage tissues from human fetal spine were used as a surrogate control. Special attention was given to genes responsible for growth regulation, chondrocyte differentiation, matrix synthesis, sulfation and transmembrane transport of sulfates. We performed morphological, histochemical, biochemical, and ultrastructural analysis of vertebral body growth plates . Results: Expression of genes that control chondroitin sulfate sulfation and corresponding protein synthesis was significantly lower in scoliotic specimens compared to controls. Biochemical analysis showed 1) a decrease in diffused proteoglycans in the total pool of proteoglycans; 2) a reduced level of their sulfation; 3) a reduction in the amount of chondroitin sulfate coinciding with raising the amount of keratan sulfate; and 4) reduced levels of sulfation on the concave side of the scoliotic deformity. Conclusion: The results suggested that altered expression of genes that control chondroitin sulfate sulfation and corresponding changes in protein synthesis on the concave side of vertebral body growth plates could be causal agents of the scoliotic deformity.
机译：背景：在以前的报告中，我们证明了特发性脊柱侧凸（IS）椎体生长板凹侧存在神经/神经胶质表型的细胞，并提出这种表型改变是IS的主要病因。在本研究中，我们利用III-IV IS级手术中取出的相同椎体生长板标本分析基因表达。我们建议在椎体生长板凹面观察到的表型变化可能与特定基因表达的改变有关，这反过来又损害了凹面的机械性能。方法：我们使用实时SYBR Green PCR分析法研究III-IV IS手术过程中取出的椎体生长板中的基因表达。来自人胎儿脊柱的软骨组织用作替代对照。对引起生长调节，软骨细胞分化，基质合成，硫酸化和硫酸盐跨膜转运的基因给予了特别关注。我们对椎体生长板进行了形态学，组织化学，生化和超微结构分析。结果：与对照相比，脊柱侧凸标本中控制硫酸软骨素硫酸化和相应蛋白质合成的基因表达明显降低。生化分析显示：1）蛋白聚糖总库中的蛋白聚糖弥散减少; 2）硫酸盐水平降低; 3）减少硫酸软骨素的量，同时增加硫酸角质素的量; 4）降低了脊柱侧凸畸形凹面的硫酸盐水平。结论：结果表明，控制硫酸软骨素硫酸化的基因表达的改变以及相应的椎体生长板凹侧蛋白质合成的变化可能是脊柱侧凸畸形的诱因。

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