褪黑素对成骨细胞作用的浓度依赖性机制研究

褪黑素是一种主要由松果体合成的激素，与特发性脊柱侧凸（IS）的发生和发展密切相关。但补充褪黑素能否能阻止IS发展，尚存在争议。为此我们在前期拟通过研究褪黑素对成骨细胞的影响以阐明褪黑素治疗效果的不确定性。研究发现，褪黑素对成骨细胞增值具有双重效应，低浓度促进,高浓度抑制，并存在浓度依赖性,在一定程度上说明补充褪黑素没有阻止所有畸形进展的原因很可能是由于褪黑素应用的浓度不适造成，但其作用机制不明。我们前期及其他学者的研究也表明，随着褪黑素浓度的增加，受体依赖性途径从开启到抑制，最后启动电压门控依赖性途径。由此推测褪黑素对成骨细胞作用的浓度依赖机制与G蛋白介导的钙通路和L型电压依赖性钙通道相关。本项目拟在我们前期研究基础上，从在体和离体两方面，运用分子生物学、电生理学、RNA干预等技术手段，研究褪黑素对成骨细胞作用浓度依赖的作用机制，为IS分子水平治疗提供新途径。

The melatonin secreted mainly by pineal body, has been shown to be responsible for the occurrence and development of idiopathic scoliosis, IS. Whether the supplements of melatonin can prevent the development of IS is still controversial. For this, we studied the influence of melatonin on osteoblast in the preliminary research to clarify the treatment uncertainties of melatonin. Our experiments revealed that melatonin has dual effects on osteoblast proliferation, depending on its concentration,that is, promoting in low concentration and inhibiting in high concentration. This to some extent explains the reason why the supplements of melatonin cannot prevent deformity progress may possibly due to improper melatonin concentration, but its mechanism is still unknown. Our previous and other scholars researches also showed that with the increase of the melatonin concentration, receptor dependence approach opens, inhibits and finally activates voltage dependence approach. Thus, we presume the concentration-dependent effects of melatonin is relevant with G-protein coupled receptors mediated calcium pathways and L voltage dependent calcium channel. Basing on our previous studies and applying molecular biology, electrophysiology technology and RNA interference technology, we will further reveal the role of concentration-dependent melatonin in osteoblast proliferation in vivo and in vitro, thus providing new molecular targeted therapy for IS.