Abstract
Objective. To study etiologic factors and pathogenetic mechanisms of scoliosis development. Material and Methods. We investigated vertebral body growth plates (GP) from convex and concave sides of the curve, intervertebral discs (IVD), and vertebral bone tissue – surgical material obtained from 100 patients at the age from 10 to 14 years with III–IV grade idiopathic scoliosis (IS). Structural components of the spine of 12–14 years old children obtained from the forensic medicine department were used as controls. The methods of morphohistochemistry, biochemistry, and ultrastructural analysis were used to study glycosaminoglycans (GAGs), oxidation-reduction enzymes, alkali and acid phosphatases, RNA, DNA, qualitative and quantitative composition of GAGs. The expression of proteoglycan genes of cartilage tissue and their protein products was investigated with molecular genetic assays. Results. Pathogenetic mechanism of spine deformity formation in idiopathic scoliosis was formulated. It was shown that idiopathic scoliosis development is predetermined by a disorder in regulation and synthesis of proteoglycans in vertebral GP. The decrease of chondroitin sulphate and increase of keratan sulphate components in proteoglycans indicate the change of proteoglycan spectrum in IS. The revealed keratan sulphate fraction is a result of increased expression of lumikan gene in condition of sharp decrease of aggrecan gene expression and its protein product quantity in chondroblasts of patients with III–IV grade IS. Conclusion. Alteration in aggrecan gene expression at the level of transcription and translation testifies for its involvement in scoliosis development.
Highlights
We investigated vertebral body growth plates (GP) from convex and concave sides of the curve, intervertebral discs (IVD), and vertebral bone tissue – surgical material obtained from 100 patients at the age from 10 to 14 years with III–IV grade idiopathic scoliosis (IS)
The expression of proteoglycan genes of cartilage tissue and their protein products was investigated with molecular genetic assays
The revealed keratan sulphate fraction is a result of increased expression of lumikan gene in condition of sharp decrease of aggrecan gene expression and its protein product quantity in chondroblasts of patients with III–IV grade IS
Summary
Изучение этиологических факторов и патогенетических механизмов развития сколиотической болезни. Исследованы пластинки роста (ПР) тел позвонков выпуклой и вогнутой сторон деформации, межпозвонковые диски (МПД), костная ткань тел позвонков (операционный материал) 100 больных в возрасте 10–14 лет, страдающих идиопатическим сколиозом (ИС) III–IV степени. Молекулярно-генетическими методами исследовались уровни экспрессии генов основных протеогликанов (ПГ) хрящевой ткани и их белковые продукты. Сформулирован патогенетический механизм формирования деформации позвоночника при ИС. Что в основе развития ИС лежит генетически зависимое нарушение регуляции синтеза и формирования ПГ в ПР тел позвонков. Выявленная кератансульфатсвязанная фракция является результатом повышенной экспрессии гена люмикана на фоне резкого снижения экспрессии гена агрекана и снижения количества его белкового продукта в хондробластах больных ИС III–IV степени. Изменение экспрессии гена агрекана на уровне транскрипции и трансляции свидетельствует о его причастности к развитию сколиотической болезни.
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