A. M. Zaidman, Elena L. Strokova, V. Novikov, A. Vasyura, M. Mikhailovsky, M. Sadovoy
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引用次数: 2
Abstract
Objective. To analyze the expression of candidate genes presumably responsible for the development of idiopathic scoliosis. Material and Methods. The study subjects were vertebral body growth plates of children aged 11-15 years suffering from Grade III-IV idiopathic scoliosis. Real-Time SYBR Green PCR assay was used to investigate the expression of genes responsible for growth regulation, chondrogenic differentiation, matrix formation and synthesis, and sulfation and transmembrane transport of sulfates. Results. Comparative analysis of gene expression did not give a clear answer. On the background of representative morphological and biochemical data including violation of the structural organization of cells and matrix on the concave side of deformity, presence of poorly differentiated chondroblasts, and lack of differentiation in columnar and hypertrophic structures, a sharp decline in synthetic potency of cells contradicted the data on high expression of IHH, TGFBR1, and EGFR genes, matrix proteoglycans genes ACAN, LUM, and VCAN, collagen types I and II, and of sulfation and sulfate transmembrane transport genes DTDST, CHST1, and CHST3. Expression of growth hormone receptor gene, differentiation genes SOX9 and PAX9, and link protein gene was reduced. Factor analysis of the studied genes has shown significant difference between gene expression in chondroblasts of patients with idiopathic scoliosis and that in controls. Conclusion. Complex interaction of genes under the control of the central regulatory mechanisms coordinates the periodization of gene turning on, thereby integrating the process of the spine growth. Violation of any of the factors in the complex system of morphogenesis regulation causes asymmetric growth resulting in scoliosis development.
目标。分析可能与特发性脊柱侧凸发生有关的候选基因的表达。材料和方法。研究对象为患有III-IV级特发性脊柱侧凸的11-15岁儿童的椎体生长板。Real-Time SYBR Green PCR检测了与生长调控、软骨分化、基质形成和合成、硫酸盐酸化和硫酸盐跨膜转运有关的基因的表达。结果。基因表达的对比分析并没有给出明确的答案。在具有代表性的形态学和生化数据的背景下,包括畸形凹侧细胞和基质的结构组织的破坏,存在低分化的成软骨细胞,柱状和肥大结构缺乏分化,细胞合成能力的急剧下降与IHH、TGFBR1和EGFR基因,基质蛋白聚糖基因ACAN、LUM和VCAN, I型和II型胶原蛋白的高表达数据相矛盾。硫酸化和硫酸盐跨膜转运基因DTDST、CHST1和CHST3。生长激素受体基因、分化基因SOX9和PAX9以及连接蛋白基因表达减少。对所研究基因的因子分析显示,特发性脊柱侧凸患者成软骨细胞中基因表达与对照组有显著差异。结论。在中枢调控机制的控制下,基因间复杂的相互作用协调基因开启的周期化,从而整合脊柱生长过程。在复杂的形态发生调节系统中,任何一个因素的违反都会导致不对称生长,从而导致脊柱侧凸的发展。