褪黑素作为一种内分泌激素在调控软骨代谢分化中发挥重要作用。我们研究发现褪黑素能够促进间充质干细胞(MSCs)成软骨分化(Gao W, J Pineal Res, 2014)，但具体机制尚不清楚。BMPs-Smad1/5/8信号通路是介导软骨分化发育的关键通路。我们前期预实验发现在MSCs成软骨分化中，褪黑素能够上调BMP2分子的表达、并增加Smad1/5/8的磷酸化水平，提示褪黑素能够激活该通路。因此，我们推测褪黑素可能是通过该通路调控MSCs的成软骨分化。为了探讨该科学问题，本项目拟开展以下研究:1.进一步明确在MSCs成软骨分化中，褪黑素能够激活BMPs-Smad1/5/8通路；2.探讨褪黑素是否通过该通路促进MSCs成软骨分化；3.对褪黑素如何激活该通路的信号转导机制进行研究。研究成果有望阐明褪黑素调控MSCs成软骨分化的机制，为将褪黑素应用于软骨损伤的干细胞组织工程等领域奠定基础

Melatonin (N-acetyl-5-methoxytrypta-mine), a neurohormone mainly synthesized and secreted by the pineal gland. Melatonin, is involved in a number of physiological processes. Our recent study (J Pineal Res, 2014) found that melatonin can enhance the chondrogenic differentiation of human bone marrow mesenchymal stem cells (MSCs), but the underlying mechanism is unknown. BMPs-Smad1/5/8 signaling pathway is known to play an critical role in regulating chondrogenesis. In our pre-experiments, we found that melatonin treatment can upregulate the expression of BMP2 and stimulate phosphorylation of Smad1/5/8 during the chondrogenic differentiation of human MSCs. Thus we proposed the hypothesis that melatonin may enhance chondrogenic differentiation of human MSCs via BMP-Smad1/5/8 signaling pathway. In this project, we plan to verify this hypothesis by conducting the following studies. Firstly, we will further prove that melatonin can activate BMPs-Smad1/5/8 signaling pathway. Then, we will try to identify that whether BMPs-Smad1/5/8 pathway is involved in the process of melatonin-enhanced chondrogenic differentiation of human MSCs. At last, we want to find out that through which signal transduction mechanism melatonin activates BMPs-Smad1/5/8 pathway. The goal of this project is to identify the mechanism of melatonin-enhanced MSCs chondrogenic differentiation, which can provide evidences for application of melatonin in tissue engineering of cartilage injury.