褪黑素是骨软骨发生发育、生长代谢和损伤修复的促进剂，对于骨性关节炎（OA）具有一定的治疗价值，但具体的作用机制尚不明确。本课题组发现褪黑素可以促进软骨细胞合成代谢，维持软骨细胞表型，从而发挥防治OA的作用；而ERK1/2通路与TGFβ/Smad2通路的交互作用可能介导了褪黑素的这种效应。本课题拟从三个层面展开研究，以明确褪黑素维持软骨细胞表型、防治OA的分子机制。包括：①动物模型水平：阐明褪黑素通过促进OA大鼠软骨表型维持，发挥防治OA的作用；②细胞学水平：阐明褪黑素经其膜受体介导，促进ERK1/2与Smad2的相互作用，上调TGFβ/Smad2通路活性，从而维持软骨细胞表型；③临床验证：阐明膝关节OA患者中是否存在细胞学实验发现的褪黑素通路活性的异常。最终系统阐明褪黑素防治OA的分子机制，为褪黑素作为防治OA的候选药物提供必要的理论依据，并为OA发病机制的研究提供新的思路。

Melatonin is an important promoter for development, metabolism and repair of bone and cartilage. It is supposed to have therapeutic value for osteoarthritis (OA), but the specific mechanism remained unknown. Our studies show melatonin could cure lesions of osteoarthritis by promoting anabolism and maintaining phenotype of chondrocyte. Moreover, the function of melatonin may be mediated by interaction between extracellular regulated protein kinases 1/2 (ERK1/2) and Smad2. We plan to do this research from three levels to figure out the molecular mechanism of melatonin’s therapeutical effect on OA. Firstly, we will study melatonin’s therapeutical effect of OA through maintaining phenotype of chondrocyte on rat models. Secondly, we will confirm whether melatonin could maintain the phenotype of chondrocyte by the interaction of ERK1/2 pathway and TGFβ/Smad2 pathway on cell models. Thirdly, we are going to have a look at whether there is any disorders on the pathways related to melatonin in OA patients. Through these, we can manifest the mechanism of melatonin’s effect on maitaining chondrocyte’s phenotype, providing theoretical foundation for melatonin as a candidate drug for OA and offering new explanations to the pathogenesis of OA.