Abstract
It is well-documented that melatonin deficiency has been linked to the etiopathogenesis of adolescent idiopathic scoliosis. In this study, we intended to apply melatonin in melatonin-deficient mice to ascertain whether melatonin could reduce the incidence/severity of scoliosis, and investigate the role of melatonin on bone mineral density in scoliosis. A total of 80 mice were divided into 4 groups: 20 quadrupedal mice and 20 bipedal mice served as controls; 20 quadrupedal and 20 bipedal mice received oral melatonin (8 mg/kg BW) daily. After 5th, 10th, 15th and 20th weeks of treatment, radiographs and in vivo micro-CT were used to determine the incidence of scoliosis and bone qualities, respectively. Upon sacrifice, the levels of melatonin were measured in each group. At 20th week, the occurrence of scoliosis was 80%, 30%, 22% and 5% in bipedal, quadrupedal, bipedal + melatonin and quadrupedal + melatonin group, respectively. The trabecular bone quality of the vertebral body was significantly ameliorated in the melatonin-treated bipedal models. Likewise, the number of osteoclasts was significantly less in those treated with melatonin. Our results indicated that melatonin deficiency may be crucial for scoliotic development, and restoration of melatonin levels can prevent scoliotic development with the improvement in bone density.
Highlights
Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine which occurs mainly in girls between the ages of 10 to 181
In Machida’ study, none of the 30 bipedal mice receiving melatonin treatment (8 mg/kg BW/day) developed scoliosis, whereas 29 out of 30 (97%) bipedal mice without receiving melatonin treatment developed scoliosis. These findings suggest that reduced levels of melatonin in bipedal mice could play a crucial role in the development of scoliosis, and the restoration of the melatonin levels by melatonin treatment prevented the development of scoliosis
The total number of osteocytes, but not the osteoblast count, was significantly abated in the pinealectomized group compared to the group with an intact pineal but there was no significant difference in the total number of osteoblasts between the two groups
Summary
Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of the spine which occurs mainly in girls between the ages of 10 to 181. In 2006, Machida et al.[17] introduced bipedal ambulation of the melatonin-deficient C57BL/6J mice as a new experimental model for AIS research. Many studies have shown a naturally occurrence of low BMD in C57BL/6J mice when compared with various inbred mouse species. This trait render an ideal candidates for assessing the effect of melatonin on bone formation in vivo. The aim of this study is to investigate the micro-structural properties of the vertebrae and demonstrate the effects of exogenous melatonin on the abnormal bone density and qualities in the bipedal C57BL/6J mouse model
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