Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Estrogen promotes the onset and development of idiopathic scoliosis via disproportionate endochondral ossification of the anterior and posterior column in a bipedal rat model

  • Zheng, Shuhui (Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Zhou, Hang (Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Gao, Bo (Department of Orthopaedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University) ;
  • Li, Yongyong (Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Liao, Zhiheng (Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Zhou, Taifeng (Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Lian, Chengjie (Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Wu, Zizhao (Department of Orthopaedics, Sun Yat-sen Memorial Hospital of Sun Yat-sen University) ;
  • Su, Deying (Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Wang, Tingting (Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Su, Peiqiang (Department of Orthopedics, The First Affiliated Hospital of Sun Yat-sen University) ;
  • Xu, Caixia (Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University)
  • Received : 2018.02.02
  • Accepted : 2018.06.27
  • Published : 2018.11.30
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Abstract

This study aimed to verify the effects of estrogen on the onset and development of adolescent idiopathic scoliosis and the mechanisms associated with these effects by constructing a pubescent bipedal rat model. Experiments were conducted to investigate whether scoliosis progression was prevented by a Triptorelin treatment. One hundred twenty bipedal rats were divided into female, OVX (ovariectomy), OVX + E2, Triptorelin, sham, and male groups. According to a spinal radiographic analysis, the scoliosis rates and curve severity of the female and OVX + E2 groups were higher than those in the OVX, Triptorelin, and male groups. The measurements obtained from the sagittal plane of thoracic vertebrae CT confirmed a relatively slower growth of the anterior elements and a faster growth of the posterior elements between T11 and T13 in the female and OVX + E2 groups than in the OVX and Triptorelin groups. Histomorphometry and immunohistochemistry revealed a significantly longer hypertrophic zone of the vertebral cartilage growth plates that expressed more type X collagen and less type II collagen in the OVX and Triptorelin groups than in the female and OVX + E2 groups. Ki67 immunostaining confirmed an increase in the proliferation of vertebral growth plate chondrocytes in the OVX group compared with the female and OVX + E2 groups. In conclusion, estrogen obviously increased the incidence of scoliosis and curve severity in pubescent bipedal rats. The underlying mechanism may be a loss of coupling of the endochondral ossification between the anterior and posterior columns. Triptorelin decreased the incidence of scoliosis and curve magnitudes in bipedal female rats.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China, Guangdong Natural Science Foundation

References

  1. Ahn, U. M. et al. The etiology of adolescent idiopathic scoliosis. Am. J. Orthop. 31, 387-395 (2002).
  2. Lowe, T. G., Edgar, M., Margulies, J. Y., Miller, N. H., Raso, V. J. & Reinker, K. A. Etiology of idiopathic scoliosis: current trends in research. J. Bone Jt. Surg. Am. 82-A, 1157-1168 (2000).
  3. Akel, I., Demirkiran, G., Alanay, A., Karahan, S., Marcucio, R. & Acaroglu, E. The effect of calmodulin antagonists on scoliosis: bipedal C57BL/6 mice model. Eur. Spine J. 18, 499-505 (2009). https://doi.org/10.1007/s00586-009-0912-1
  4. Cowell, H. R., Hall, J. N. & MacEwen, G. D. Genetic aspects of idiopathic scoliosis. Clin. Orthop. Relat. Res. 86, 121-131 (1972). https://doi.org/10.1097/00003086-197207000-00018
  5. Fischer, R. L. & DeGeorge, F. V. Idiopathic scoliosis: an investigation of genetic and environmental factors. J. Bone Jt. Surg. 49, 1005-1006 (1976).
  6. Kazmin, A. I. & Merkorieva, R. V. Role of disturbance of glucosaminoglycaine metabolism in the pathogenesis of scoliosis. Ortop. Travmatol. Protez. 32, 87-91 (1971).
  7. Pedrini, V. A., Ponset, I. V. & Dohrman, S. C. Glycosaminoglycans of intervertebral disc in idiopathic scoliosis. J. Lab. Clin. Med. 82, 938-950 (1973).
  8. Dickson, R. A., Lawton, J. O., Archer, I. A. & Butt, W. P. The pathogenesis of idiopathic scoliosis: biplanar spinal asymmetry. J. Bone Jt. Surg. Br. 66, 8-15 (1984).
  9. Schultz, A. B. A biomechanical view of scoliosis. Spine 1, 162-171 (1976). https://doi.org/10.1097/00007632-197609000-00007
  10. Bararack, R. L., Wyatt, M. P., Whitecloud, T. S., Burk, S. W., Robert, J. W. & Brinker, M. R. Vibratory hypersensitivity in idiopathic scoliosis. J. Pediatr. Orthop. 8, 389-395 (1988). https://doi.org/10.1097/01241398-198807000-00002
  11. Chuma, A., Kitahara, H., Minami, S., Goto, S., Takaso, M. & Moriya, H. Structural scoliosis model in dogs with experimentally induced syringomyelia. Spine 22, 589-594 (1997). https://doi.org/10.1097/00007632-199703150-00002
  12. Kindsfater, K., Lowe, T., Lawellin, D., Weinstein, D. & Akmakjian, J. Levels of platelet calmodulin for the prediction of progression and severity of adolescent idiopathic scoliosis. J. Bone Jt. Surg. 76, 1186-1192 (1994). https://doi.org/10.2106/00004623-199408000-00009
  13. Letellier, K. et al. Estrogen cross-talk with the melatonin signaling pathway in human osteoblasts derived from adolescent idiopathic scoliosis patients. J. Pineal Res. 45, 383-393 (2008). https://doi.org/10.1111/j.1600-079X.2008.00603.x
  14. Leboeuf, D., Letellier, K., Alos, N., Edery, P. & Moldovan, F. Do estrogens impact adolescent idiopathic scoliosis? Trends Endocrinol. Metab. 20, 147-152 (2009). https://doi.org/10.1016/j.tem.2008.12.004
  15. Iwamuro, S. et al. Teratogenic and anti-metamorphic effects of bisphenol A on embryonic and larval Xenopus laevis. Gen. Comp. Endocrinol. 133, 189-198 (2003). https://doi.org/10.1016/S0016-6480(03)00188-6
  16. Kulis, A. et al. Participation of sex hormones in multifactorial pathogenesis of adolescent idiopathic scoliosis. Int. Orthop. 39, 1227-1236 (2015). https://doi.org/10.1007/s00264-015-2742-6
  17. Man, G. C. et al. A review of pinealectomy-induced melatonin-deficient animal models for the study of etiopathogenesis of adolescent idiopathic scoliosis. Int. J. Mol. Sci. 15, 16484-16499 (2014). https://doi.org/10.3390/ijms150916484
  18. Wu, T. et al. Role of enhanced central leptin activity in a Scoliosis model created in bipedal amputated mice. Spine (Phila. Pa 1976) 40, E1041-E1045 (2015). https://doi.org/10.1097/BRS.0000000000001060
  19. Dede, O., Akel, I., Demirkiran, G., Yalcin, N., Marcucio, R. & Acaroglu, E. Is decreased bone mineral density associated with development of scoliosis? A bipedal osteopenic rat model. Scoliosis 6, 24 (2011). https://doi.org/10.1186/1748-7161-6-24
  20. Guo, X., Chau, W. W., Chan, Y. L. & Cheng, J. C. Relative anterior spinal overgrowth in adolescent idiopathic scoliosis. Results of disproportionate endochondral-membranous bone growth. J. Bone Jt. Surg. Br. 85, 1026-1031 (2003).
  21. Xiong, B., Sevastik, B., Willers, U., Sevastick, J. & Hedlund, R. Structural vertebral changes in the horizontal plane in idiopathic scoliosis and the long-term corrective effect of spine instrumentation. Eur. Spine J. 4, 11-14 (1995). https://doi.org/10.1007/BF00298411
  22. Haas, S. L. Growth in length of the vertebrae. Arch. Surg. Chic. 38, 245-249 (1939). https://doi.org/10.1001/archsurg.1939.01200080057004
  23. Leone Roberti Maggiore, U. et al. Triptorelin for the treatment of endometriosis. Expert Opin. Pharmacother. 15, 1153-1179 (2014). https://doi.org/10.1517/14656566.2014.916279
  24. Boudreau, M. et al. Utility of morphological abnormalities during early-life development of the estuarine mummichog, Fundulus heteroclitus, as an indicator of estrogenic and anti estrogenic endocrine disruption. Environ. Toxicol. Chem. 23, 415-425 (2004). https://doi.org/10.1897/03-50
  25. Sanders, J. O., Browne, R. H., McConnell, S. J., Margraf, S. A., Cooney, T. E. & Finegold, D. N. Maturity assessment and curve progression in girls with idiopathic scoliosis. J. Bone Jt. Surg. Am. 89, 64-73 (2007). https://doi.org/10.2106/JBJS.F.00067
  26. Raczkowski, J. W. The concentrations of testosterone and estradiol in girls with adolescent idiopathic scoliosis. Neuroendocrinol. Lett. 28, 302-304 (2007).
  27. Demirkiran, G., Dede, O., Yalcin, N., Akel, I., Marcucio, R. & Acaroglu, E. Selective estrogen receptor modulation prevents scoliotic curve progression: radiologic and histomorphometric study on a bipedal C57Bl6 mice model. Eur. Spine J. 23, 455-462 (2014). https://doi.org/10.1007/s00586-013-3072-2
  28. Kronenberg, H. M. Developmental regulation of the growth plate. Nature 423, 332-336 (2003). https://doi.org/10.1038/nature01657
  29. Farnum, Cornelia, E., Wilsman & Norman, J. Converting a differentiation cascade into longitudinal growth: stereology and analysis of transgenic animals as tools for understanding growth plate function. Curr. Opin. Orthop. 12, 428-433 (2001). https://doi.org/10.1097/00001433-200110000-00011
  30. Zhang, H. et al. Intramembranous ossification and endochondral ossification are impaired differently between glucocorticoid-induced osteoporosis and estrogen deficiency-induced osteoporosis. Sci. Rep. 8, 3867 (2018). https://doi.org/10.1038/s41598-018-22095-1
  31. Nilsson, O., Marino, R., De Luca, F., Phillip, M. & Baron, J. Endocrine regulation of the growth plate. Horm. Res. 64, 157-165 (2005).
  32. Illien-Junger, S., Torre, O. M., Kindschuh, W. F., Chen, X., Laudier, D. M. & Iatridis, J. C. AGEs induce ectopic endochondral ossification in intervertebral discs. Eur. Cell. Mater. 32, 257-270 (2016). https://doi.org/10.22203/eCM.v032a17
  33. Borjesson, A. E. et al. The role o-f estrogen receptor ${\alpha}$ in growth plate cartilage for longitudinal bone growth. J. Bone Miner. Res. 25, 2690-2700 (2010). https://doi.org/10.1002/jbmr.156
  34. Zhu, F., Qiu, Y., Yeung, H. Y., Lee, K. M. & Cheng, J. C. Histomorphometric study of the spinal growth plates in idiopathic scoliosis and congenital scoliosis. Pediatr. Int. 48, 591-598 (2006). https://doi.org/10.1111/j.1442-200X.2006.02277.x

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