The mode of Scheuermann's disease inheritance and its phenotypic traits in probands and their relatives were studied in 90 pedigrees (90 probands and 385 relatives). The disorder was identified as a genetically related pathology inherited by autosomal dominant type, controlled by a mutant major gene, as a kyphotic deformity without signs of vertebral bodies' anomaly and torsion. Morphological and biochemical studies showed disturbance in the structure of vertebral growth plate anterior aspects at the level of deformity, defects in proliferation and differentiation of chondrocytes, and change in proteoglycan spectrum in cells and matrix. Twelve candidate genes were studied in chondrocytes isolated from vertebral growth plates of patients with Scheuermann's disease. The study results included disorder in the IHH gene expression and preservation of the expression of PAX1, two aggrecan isoforms, link protein, types I and II collagen, lumican, versican, growth hormone and growth factor receptor genes, and proliferation gene. Preservation of the SOX9 gene (transcription gene) probably indicates posttranscriptional genetic disorders. The study is under way.

Idiopathic scoliosis is one of the most common disabling pathologies of children and adolescents. Etiology and pathogenesis of idiopathic scoliosis remain unknown. To study the etiology of this disease we identified the cells' phenotypes in the vertebral body growth plates in patients with idiopathic scoliosis.Materials and methods: The cells were isolated from vertebral body growth plates of the convex and concave sides of the deformity harvested intraoperatively in 50 patients with scoliosis. Cells were cultured and identified by methods of common morphology, neuromorphology, electron microscopy, immunohistochemistry and PCR analysis.Results: Cultured cells of convex side of deformation were identified as chondroblasts. Cells isolated from the growth plates of the concave side of the deformation showed numerous features of neuro- and glioblasts. These cells formed synapses, contain neurofilaments, and expressed neural and glial proteins.Conclusion: For the first time we demonstrated the presence of cells with neural/glial phenotype in the concave side of the vertebral body growth plate in scoliotic deformity. We hypothesized that neural and glial cells observed in the growth plates of the vertebral bodies represent derivatives of neural crest cells deposited in somites due to alterations in their migratory pathway during embryogenesis. We also propose that ectopic localization of cells derived from neural crest in the growth plate of the vertebral bodies is the main etiological factor of the scoliotic disease.

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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.

To identify cell phenotypes in vertebral body growth plates from patients with idiopathic scoliosis. Material and Methods. Cells were isolated from vertebral body growth plates both on convex and concave sides of the deformity in patients operated on for scoliosis. Cells were cultured and identified by methods of common morphology, neuromorphology, electron microscopy, immunohistochemistry, and PCR analysis. Results. Cultured cells obtained from the convex side of the deformity were identified as chondroblasts. Cells isolated from growth plates on the concave side of the deformity were described as neuroand glioblasts. Cells formed synapses, contained neurofilaments, and expressed neural and glial proteins, respectively. Conclusion. Ectopic localization of neural crest-derived cells in vertebral body growth plates is the etiological factor for scoliotic disease.