中国骨质疏松杂志

5-羟色胺对骨骼代谢的调控机制研究进展

Research Progress on the Regulation Mechanisms of serotonin on Bone Metabolism

DOI：10.3969/j.issn.1006.7108.2022.04.019

中文关键词: 中枢5-HT 外周5-HT 5-HT受体 LP533401 骨组织代谢骨质疏松

英文关键词:central serotonin peripheral serotonin serotonin receptors LP533401 bone metabolism osteoporosis

基金项目:兰州市2018年第三批科技计划项目 (2018-3-79)；国家自然青年科学基金项目（31801194）

作者	单位
张芮浩1,2 张晓勃1,2 袁文欢4 胡一村 1,2 陈祥义1,2 于得臣1,2 齐进1,2 周海宇1,3*	1.兰州大学第二医院骨科，甘肃兰州 730030 2.甘肃省骨关节疾病研究重点实验室，甘肃兰州 730030 3.兰州市西固区人民医院，甘肃兰州 730000； 4.内蒙古科技大学包头一附院，内蒙古包头014000

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中文摘要:

5-HT与骨组织代谢密切相关，中枢5-HT可以促进骨生成，抑制骨吸收，而外周5-HT可以促进骨吸收。外周5-HT直接作用于成骨细胞的5-HT1b受体，抑制FOXO1和CREB的结合，促进FOXO1与ATF4结合，并抑制成骨细胞内的细胞周期基因CYCD1、D2和E1，抑制成骨细胞增殖。Lrp5可抑制Tph1的表达和外周5-HT表达，促进骨生成。中枢5-HT可作用于下丘脑腹内侧核神经元的5-HT2c受体，激活CAM信号通路，促进CREB磷酸化，抑制交感神经活性，从而抑制RANKL表达，抑制骨吸收，促进骨生成。而瘦素可作用于血清素能神经元上的瘦素受体，抑制中枢5-HT合成，促进骨吸收。此外，5-HT2a，5-HT2b，5-HT6受体也参与了对骨组织的调控。Tph1抑制剂LP533401可以改善去卵巢小鼠的骨质流失。体内中枢5-HT促进骨生成和外周5-HT抑制骨生成的作用相平衡，提示有某种反馈机制将两者相联系，这为探究骨质疏松的发生机制和临床治疗骨质疏松提供了新的思路。

英文摘要:

Serotonin is closely related to bone metabolism. Central serotonin promotes bone formation and inhibits bone resorption whereas peripheral serotonin promotes bone resorption. Peripheral serotonin acts on the 5-HT1b receptors of osteoblasts, inhibits the binding of FOXO1 and CREB whereas promotes the binding of FOXO1 and ATF4, further inhibiting the cell cycle genes CYCD1, D2 and E1 in osteoblasts and the proliferation of osteoblasts. Lrp5 inhibits the Tph1 expression and the content of peripheral serotonin whereas promotes bone formation. Central serotonin acts on 5-HT2c receptors in ventromedial hypothalamic nucleus neurons, activates CAM signal pathway and promotes CREB phosphorylation whereas inhibits sympathetic activity, RANKL expression and bone resorption. Leptin acts on the leptin receptors in serotonergic neurons, inhibits the synthesis of central serotonin and bone formation. In addition, 5-HT2a receptors, 5-HT2b receptors and 5-HT6 receptors are also involved in the regulation of bone tissue. Tph1 inhibitor LP533401 improves bone loss in ovariectomized mice. The role of central serotonin in promoting bone formation and the role of peripheral serotonin in promoting bone resorption are balanced in vivo, suggesting that there are some unknown feedback mechanisms connecting them, which provides us new research and clinical treatment ideas for osteoporosis.

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