褪黑素浓度依赖性调控ZFAS1介导成骨细胞增殖的机制研究

褪黑素与骨质疏松症、特发性脊柱侧凸及骨肉瘤的发生发展密切相关。我们前期研究发现，褪黑素通过细胞质内钙通道对成骨细胞增殖具有双重效应，低浓度促进，高浓度抑制，存在浓度依赖性，但细胞核内调控机制尚不明确。我们的前期研究表明褪黑素浓度依赖性调控成骨细胞增殖与非编码RNA调控相关。由此提出，ceRNA调控和miRNA调控两种途径介导褪黑素调控成骨细胞增殖，随着褪黑素浓度的增加，ceRNA调控通路由促进转为抑制，更高浓度时，激活miRNA途径。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、RNA干预等技术手段，进一步研究褪黑素调控成骨细胞增殖的机制，确定褪黑素特异性靶点，为增强褪黑素药理作用，临床治疗骨代谢疾病奠定基础。

Melatonin is closely related to the occurrence and development of osteoporosis, idiopathic scoliosis and osteosarcoma. Our previous study found that melatonin has a dual effect on osteoblastic proliferation through the cytoplasmic calcium channel. There is a concentration-dependent that low concentration promote the proliferation of osteoblast while high concentration inhibition, but the regulatory mechanism in the nucleus is not clear. Our studies showed that the concentration-dependent regulation of melatonin on osteoblast proliferation is related to non-coding RNA regulation. Therefore, we propose that both ceRNA regulation and miRNA regulation mediated melatonin-regulated osteoblast proliferation, with the increase of melatonin concentration,ceRNA regulate pathway turn promotion into inhibition when the concentration is higher, miRNA pathway is activated. This project is intended to further study the mechanism of melatonin in regulating osteoblast proliferation based on our previous studies, and determine melatonin-specific target point using molecular biology and RNA interference in vitro and in vivo, to enhance the pharmacological effects of melatonin, laid the foundation for clinical treatment of bone metabolism diseases.