| Objective: Adolescent idiopathic scoliosis(AIS)was a three-dimensional spinal deformity which was found in otherwise healthy 10-year-old adolescent.The disease was more prevalent in girls.Currently the pathogenesis and etiology of AIS was not understood sufficiently.There had been a lot of hypothesis which had not yet been clearly demonstrated.In recent years,osteopontin(OPN)was paid more attentions to as the potential causes of adolescent idiopathic scoliosis.This paper intended to establish a creative bipedal mouse model with high OPN level to observe the differences in terms of the severity and scoliosis incidence between high OPN groups and the controls.The date of OPN concentration in mouse serum was evaluated to determine whether elevated OPN level can directly induce scoliosis.On the basis of this model,we established a kind of AIS model with high osteopontin level in bipedal female mice.The scoliosis incidence and severity was assessed to demonstrate whether it can be used as a novel drug intervention model in AIS.Methods:(1)120 matched-year C3 Heej male mice with similar weight were chosen and then randomly divided into three groups.Amputation of forelimbs and tail was performed on two groups at the age of 3 weeks.Then one group after operation was given intraperitoneal injection of high concentration of OPN while the other two groups were treated with saline.All of three groups were placed in special cages to induce upright posture for 3 months.Animal X-ray was taken to determine the incidence and severity of scoliosis.The mice serum was measured by an ELISA assay to determine the difference of OPN concentration among three groups at the same time.(2)Twenty female C3 Heej mice and twenty male matched mice were chosen as the group of high OPN female mice and the group of high OPN male mice.Another twenty male and twenty female C3 Heej mice were defined as control male mice and control female mice.Four groups of mice were induced to scoliosis for three months by the same way.Animal X-ray was also taken to determine the incidence and severity of scoliosis.Results:(1)There were groups of high OPN bipedal mice,control bipedal mice and control quadruped mice.The circulating OPN concentration were 207.3±85.1ng/ml,74.6±20.1ng/ml and 83.7±32.2 ng/ml,respectively.The circulating OPN concentration of the mice in high OPN mice was significantly increased after 3 month.The average body length were(13.6±1.0)cm,(13.9±0.9)cm and(13.6±0.9)cm,respectively.The Cobb angle were(29.8±6.1)°,(20.1±4.4)° and(16.6±2.9)°,respectively.The incidence of scoliosis were 92.5%,52.1% and 12.5%,respectively.No significant difference of body length was found amongst all groups.The incidence of scoliosis and curve magnitude were statistically significantly more aggravated in high OPN mice than the controls.(2)There were groups of high OPN female bipedal mice,high OPN male bipedal mice,control bipedal female mice and control bipedal male mice.The Cobb angle were(25.8±6.7)°,(20.9±6.8)°,(15.6±3.1)° and(17.1±4.5)°,respectively.The incidence of scoliosis were 90%,80%,40% and 45%,respectively.High OPN female mice and high OPN male mice had significantly higher incidence of scoliosis than the controls,whereas the curve magnitude of high OPN female mice was significantly severer than high OPN male mice.Conclusion: Our work revealed that high OPN levels might play an important role in the pathogenesis of AIS in animal models.It not only increases the risk of scoliosis in bipedal mice,but also contribute to the curve deterioration.The experimental results demonstrated the high OPN to be a key factor in the onset and progression of AIS.A higher scoliosis incidence and more severe curves were observed in female bipedal mice compared with male bipedal mice and controls.As AIS had a high incidence in female,the model of female bipedal amputated mouse with high OPN level can be used as a better animal model in the research of idiopathic scoliosis. |
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