GENE EXPRESSION IN GROWTH PLATE CHONDROCYTES OF PATIENTS WITH IDIOPATHIC SCOLIOSIS

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.