【摘要】 血清素5羟色胺(5-HT)是一种古老的神经递质,表达于全身各组织,具有广泛而复杂的生理功能。近年研究发现,外周血清素可以介导低密度脂蛋白受体相关蛋白5(LRP5),参与动物骨量和骨形成调节。LRP5通过特异性抑制十二指肠嗜铬细胞合成血清素,降低血液血清素水平。血液中血清素可以通过成骨细胞上的5-HT1B型受体,经蛋白激酶A-环磷酸腺苷(PKA-cAMP)途径影响转录因子cAMP反应元件结合蛋白(CREB)的磷酸化,抑制成骨细胞周期蛋白Cyclin D1、D2和E1的表达而抑制其增殖作用,进而抑制骨形成。以此通路的特异性分子为靶点的药物(如抑制血清素合成的药物)可以对骨形成进行调节,为骨质疏松等骨代谢性疾病的治疗提供新的研究方向。更多还原

【Abstract】 As an ancient neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) is expressed in various tissues of the body and has broad and complex physiological functions. It is found in recent years that peripheral serotonin can mediate the effect of low density lipoprotein receptor-related protein 5 (LRP5) on animal bone mass and bone formation parameters.LRP5 can reduce blood serotonin level via specifically inhibiting synthesis of serotonin by duodenal chromaffin cells. Serotonin in the circulation can activate protein kinase A-cyclic adenosine monophosphate(PKA-cAMP) signaling pathway after binding to 5-HT1B receptor on the osteoblast. Then cAMP response element binding protein (CREB) phosphorylation is affected, followed by down-regulation of expression of cyclin D1, D2 and E1. Accordingly, serotonin inhibits bone formation. Drugs targeting specific molecules in this pathway (such as drugs of inhibiting serotonin synthesis) could regulate bone formation, which provides a new research direction towards the treatment of osteoporosis and other bone metabolic diseases更多还原