A scoliosis model of bipedal female mouse induced by high-concentration osteopontin

doi:10.3969/j.issn.2095-4344.2016.49.001

Abstract

Abstract:

BACKGROUND: In recent years, the relevant research confirmed that increased levels of osteopontin may lead to the development of adolescent idiopathic scoliosis. The establishment of appropriate animal models of adolescent idiopathic scoliosis is of great significance in the research and treatment of such diseases.
OBJECTIVE: To observe the occurrence of scoliosis of the bipedal female mice induced by high concentration of osteopontin, and provide evidence for establishing ideal drug models of adolescent idiopathic scoliosis.
METHODS: C3H/HeJ mice of the same age were selected and randomly assigned to high-concentration osteopontin female mice (n=20) and male mice (n=20). This study also set control male mice group (n=20) and control female mice group (n=20). Mice aged 3 weeks from four groups were subjected to upper limb amputation and rat tail resection to establish bipedal mouse models. After surgery, a special cage was used to induce the upright state. High-concentration osteopontin female mice and male mice were daily intraperitoneally injected with high-concentration osteopontin (40 μg/kg). Mice in the control group were intraperitoneally injected with physiological saline. At 3 months after induction, animal spine X-ray examination was conducted to measure Cobb angle. If Cobb angle was greater than 10°, a successful induction was set. The incidence and severity of scoliosis were evaluated.
RESULTS AND CONCLUSION: (1) In the high-concentration osteopontin female mice group, scoliosis was observed in 18 mice. Cobb angle was 16°-38°, averagely (25.8±6.7)°. In the high-concentration osteopontin male mice group, scoliosis was observed in 16 mice. Cobb angle was 11°-34°, averagely (20.9±6.8)°. In the control male mice group, scoliosis was observed in 8 mice. Cobb angle was 12°-21°, averagely (15.6±3.1)°. In the control female mice group, scoliosis was observed in 9 mice. Cobb angle was 11°-24°, averagely (17.1±4.5)°. (2) The incidence of scoliosis was significantly higher in the high-concentration osteopontin female and male mice groups than in the control female and male mice groups (P < 0.05). No significant difference in the incidence of scoliosis was detected between high-concentration osteopontin female and male mice groups (P > 0.05). However, curve magnitude was significantly severer in the high-concentration osteopontin female mice group than in the high-concentration osteopontin male mice group (P < 0.05). (3) Results suggested that the scoliosis incidence was higher and scoliosis was severer in high-concentration osteopontin-induced bipedal mice, which was more closed to human.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

Key words: Osteopontin, Scoliosis, Female, Tissue Engineering

CLC Number:

R318

Tang Feng, Xie Ning, Wu Tao, Liu Jun, Wang Bin-bin, Wang Yang, Xu Li-zhang. A scoliosis model of bipedal female mouse induced by high-concentration osteopontin[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(49): 7301-7306.

Figures/Tables 2

References

[1] Hefti F. Pathogenesis and biomechanics of adolescent idiopathic scoliosis (AIS). J Child Orthop. 2013;7(1): 17-24.
[2] Weinstein SL, Dolan LA, Cheng JC, et al. Adolescent idiopathic scoliosis. Lancet. 2008;371(9623):1527-1537.
[3] Machida M, Saito M, Dubousset J, et al. Pathological mechanism of idiopathic scoliosis: experimental scoliosis in pinealectomized rats. Eur Spine J. 2005; 14(9):843-848.
[4] Oyama J, Murai I, Kanazawa K, et al. Bipedal ambulation induces experimental scoliosis in C57BL/6J mice with reduced plasma and pineal melatonin levels. J Pineal Res. 2006;40(3):219-224.
[5] de Sèze M, Cugy E. Pathogenesis of idiopathic scoliosis: a review. Ann Phys Rehabil Med. 2012; 55(2):128-138.
[6] Asou Y, Rittling SR, Yoshitake H, et al. Osteopontin facilitates angiogenesis, accumulation of osteoclasts, and resorption in ectopic bone. Endocrinology. 2001; 142(3):1325-1332.
[7] Kojima H, Uede T, Uemura T. In vitro and in vivo effects of the overexpression of osteopontin on osteoblast differentiation using a recombinant adenoviral vector. J Biochem. 2004;136(3):377-386.
[8] Narisawa S, Yadav MC, Millán JL. In vivo overexpression of tissue-nonspecific alkaline phosphatase increases skeletal mineralization and affects the phosphorylation status of osteopontin. J Bone Miner Res. 2013;28(7):1587-1598.
[9] Yadav MC, Huesa C, Narisawa S, et al. Ablation of osteopontin improves the skeletal phenotype of phospho1(-/-) mice. J Bone Miner Res. 2014;29(11): 2369-2381.
[10] Moreau A, Franco A, Azeddine B, et al. High circulating levels of osteopontin are associated with idiopathic scoliosis onset and spinal deformity progression: Paper# 79. Spine Journal Meeting Abstracts: LWW, 2009:109.
[11] Sun GQ, Lam TP, Bobby NG, et al. High osteopontin plasma level associated with abnormal cortical bone mineral density in girls with adolescent idiopathic scoliosis. Studies in Health Technology & Informatics. 2012; 176(1):457.
[12] Xie N, Li M, Wu T, et al. Does elevated osteopontin level play an important role in the development of scoliosis in bipedal mice. Spine J. 2015;15(7): 1660-1664.
[13] Machida M, Dubousset J, Imamura Y, et al. An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine(Phila Pa 1976). 1993;18(12): 1609-1615.
[14] Dubousset J, Queneau P, Thillard MJ. Experimental scoliosis induced by pineal and diencephalic lesions in young chickens: Its relation with clinical findings. Orthop Trans. 1983;7(7):4.
[15] Kanemura T, Kawakami N, Deguchi M, et al. Natural course of experimental scoliosis in pinealectomized chickens. Spine (Phila Pa 1976). 1997;22(14):1563-1567.
[16] Nette F, Dolynchuk K, Wang X, et al. The effects of exposure to intense, 24 h light on the development of scoliosis in young chickens. Stud Health Technol Inform. 2002;91:1-6.
[17] 肖军,吴志宏,邱贵兴,等. 直立姿势对脊柱侧凸易感性及侧凸曲线进展规律的影响[J].中华医学杂志, 2007,87(1): 48-52.
[18] Cheung KM, Wang T, Poon AM, et al. The effect of pinealectomy on scoliosis development in young nonhuman primates. Spine (Phila Pa 1976). 2005; 30(18):2009-2013.
[19] 邱贵兴,肖军,吴志宏,等. 双足鼠直立姿势相关因素及促直立的措施[J].中华实验外科杂志, 2006,23(6):734-736.
[20] Leboeuf D, Letellier K, Alos N, et al. Do estrogens impact adolescent idiopathic scoliosis. Trends Endocrinol Metab. 2009;20(4):147-152.
[21] Warren MP, Brooks-Gunn J, Hamilton LH, et al. Scoliosis and fractures in young ballet dancers. Relation to delayed menarche and secondary amenorrhea. N Engl J Med. 1986;314(21):1348-1353.
[22] Janusz P, Kotwicka M, Andrusiewicz M,et al. Estrogen receptors genes polymorphisms and age at menarche in idiopathic scoliosis.BMC Musculoskelet Disord. 2014;15:383.
[23] Fendri K, Patten S, Zaouter C,et al. Recent advances in the study of candidate genes for adolescent idiopathic scoliosis. Stud Health Technol Inform. 2010;158:3-7.
[24] Inoue M, Minami S, Nakata Y, et al. Association between estrogen receptor gene polymorphisms and curve severity of idiopathic scoliosis. Spine (Phila Pa 1976). 2002;27(21):2357-2362.
[25] Rusin B, Kotwicki T, G?odek A,et al. Estrogen receptor 2 expression in back muscles of girls with idiopathic scoliosis - relation to radiological parameters. Stud Health Technol Inform. 2012;176:59-62.