ETIOLOGY AND PATHOGENESIS OF IDIOPATHIC SCOLIOSIS

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.

1. Абальмасова Е.А. К этиологии боковых искривлений позвоночника у детей и подростков // I Всесоюз. съезд травматол.-ортопедов: Тез. докл. М., 1965. С. 218–220.

2. Аксенович Т.И., Зайдман А.М., Зоркольцева И.В. и др. Новые модели наследования сложных признаков и их исследования при сегрегационном анализе идиопатического сколиоза // Генетика. 1999. Т. 35. № 2. С. 255–262.

3. Васильев Ю.М., Маленков А.Г. Клеточная поверхность и реакция клетки. Л., 1968.

4. Дудин М.Г. Идиопатический сколиоз и директивные системы организма // Адаптация различных систем организма при сколиотической деформации позвоночника: Методы лечения: Тез. докл. Междунар. симпозиума. М., 2003. С. 26–27.

5. Дудин М.Г. Идиопатический сколиоз: Фронтальная дуга // Адаптация различных систем организма при сколиотической деформации позвоночника: Методы лечения: Тез. докл. Междунар. симпозиума. М., 2003. С. 23–25.

6. Зайдман А.М. Идиопатический сколиоз. Новосибирск, 1994.

7. Зайдман А.М., Корель А.В., Сахаров А.В. и др. Структурно-функциональные особенности пластинки роста тела позвонка человека при идиопатическом сколиозе // Хирургия позвоночника. 2004. № 2. С. 64–73.

8. Зайдман А.М., Корель А.В., Сахаров А.В. и др. Морфогенез болезни Шейерманна – Мау // Хирургия позвоночника. 2005. № 2. С. 73–83.

9. Конюхов Б.В. Биологическое моделирование наследственных болезней человека. М., 1969.

10. Корочкин Л.И. Взаимодействие генов в развитии. М., 1977.

11. Нейфах А.А., Тимофеева М.Я. Молекулярная биология процессов развития. М., 1977.

12. Цивьян Я.Л., Зайдман A.M. Морфогенез сколиоза. Новосибирск, 1978.

13. Bonaiti С., Feingold J., Briard M.L., et al. [Genetics of idiopathic scoliosis] // Helv. Paediatr. Acta. 1976. Vol. 31. P. 229–240. French.

14. Burwell R.G. The consortium approach: A problem too big for any one of us // Research into Spinal Deformities I: First Biannual Meeting of International Research Society of Spinal Deformities. IOS Press. 1997. P. 499–502.

15. Burwell R.G., Dangerfield P.H. A multifactorial concept of the causation of idiopathic scoliosis // 10th International Philip Zorab Symposium: Programme and abstracts. Oxford, 1998. P. 48.

16. Burwell R.G., Dangerfield P.H. How does skeletal growth affect the onset and progression of adolescent idiopathic scoliosis? The Red Queen concept applied to trunk growth and 3D balance. A speculation // 10th International Philip Zorab Symposium: Programme and abstracts. Oxford, 1998. P. 47–48.

17. Byers S., van Rooden J.C., Foster B.K. Structural changes in the large proteoglycan aggrecan, in different zone of the ovine growth plate // Calcified Tissue Int. 1997. Vol. 60. P.71–78.

18. Cowell H.R., Hall J.N., MacEwen G.D. Genetic aspects of idiopathic scoliosis: A Nicholas Andry award essay, 1970 // Clin. Orthop. Relat. Res. 1972. N 86. P. 121–131.

19. Dickson R.A., Lawton J.O., Archer I.A., et al. The pathogenesis of idiopathic scoliosis. Biplanar spinal asymmetry // J. Bone Joint Surg. Br. 1984. Vol. 66. P. 8–15.

20. Dietrich C.P., Nader H.B., Britto L.R.G., et al. Chemical composition of heparitin sulfate. Fractionation and characterization of four acidic mucopolysaccharides in heparitin sulfate from beef lung tissue // Biochim. Biophys. Acta. 1971. Vol. 237. P. 430–441.

21. Herman R., Maulucci R., Stuyck J., et al. Vestibular functioning in idiopathic scoliosis // Orthop. Trans. 1979. Vol. 3. P. 218.

22. Kapetanos G., Potoupnis M., Markou K., et al. Vestibular system evaluation in patients with idiopathic scoliosis by caloric stimulation // 6th Congress of the European Federation of National Associations of Orthopaedics and Traumatology: Abstract Book. Finland, 2003. P. 126.

23. Lozzo R.V. The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins // J. Biol. Chem. 1999. Vol. 274. P. 18843–18846.

24. Misol S., Ponseti I.V., Samaan N., et al. Growth hormone blood levels in patients with idiopathic scoliosis // Clin. Orthop. Relat. Res. 1971. N 81. P. 122–125.

25. Putti V. Die angeborene deformitäten der wirbelsä // Fort. A. d. Geb. D. Röntgentr. 1910. P. 14–15.

26. Riseborough E.J., Wynne-Davies R. A genetic survey of idiopathic scoliosis in Boston, Massachusetts // J. Bone Joint. Surg. Am. 1973. Vol. 55. P. 974–982.

27. Roughley P.J. Biology of intervertebral disc aging and degeneration // Spine. 2004. Vol. 29. P. 2691–2699.

28. Skogland L.B., Miller J.A. Growth related hormones in idiopathic scoliosis. An endocrine basis for accelerated growth // Acta Orthop. Scand. 1980. Vol. 51. P. 779–780.

29. Skogland L.B., Miller J.A., Skottner A., et al. Serum somatomedin A and non-dialyzable urinary hydroxyproline in girls with idiopathic scoliosis // Acta Orthop. Scand. 1981. Vol. 52. P. 307–313.

30. Theocharis A.D., Tsara M.E., Papageorgakopoulou N., et al. Characterization of glycosaminoglycans from human normal and scoliotic nasal cartilage with particular reference to dermatan sulfate // Biochim. Biophys. Acta. 2001. Vol. 1528. P. 81–88.

31. Van de Lest C.H., Versteeg E.M., Veerkamp J.H., et al. Quantification and characterization of glycosaminoglycans at the nanogram level by a combined azure A-silver staining in agarose gels // Anal. Biochem. 1994. Vol. 221. P. 356–361.

32. Yamada K., Yamamoto H., Nakagawa Y., et al. Etiology of idiopathic scoliosis // Clin. Orthop. Relat. Res. 1984. N 184. P. 50–57.