关节软骨的衰老退变与损伤降解是骨关节炎(OA)的重要病理特征，但其发生的机制尚未完全阐明。课题组在前期研究中利用蛋白质组技术筛选与软骨衰老退变有关的蛋白质，发现老年小鼠关节软骨肌球蛋白轻链3(MYL3)表达显著降低，干扰软骨细胞中MYL3后软骨降解酶类MMP13等表达显著增加，软骨合成代谢因子SOX9等表达显著下降，进行RNA测序发现MYL3与Notch信号存在一定联系，提示MYL3可能通过Notch信号参与调节关节软骨的合成及分解代谢，衰老退变乃至OA的发生。本项目拟构建可诱导、软骨细胞中敲除MYL3的小鼠与细胞模型，以明确MYL3-Notch信号在维持软骨稳态、关节软骨衰老退变与OA发生中的作用，应用RNA测序与蛋白质组学等细胞与分子生物学技术，从整体、细胞与分子水平探讨MYL3-Notch信号在软骨衰老与OA发生的中具体机制，旨在为软骨生物学提供新观点，为防治OA提供新的潜在靶点。

The senescence and degradation of articular cartilage are important pathological features of osteoarthritis (OA), but the mechanism of its occurrence has not been fully elucidated. In our previous studies, proteomic techniques were used to screen the changing proteins related to cartilage senescence and degeneration. We noticed that the expression of myosin light chain 3 (MYL3) in articular cartilage of aged mice was significantly decreased. Interfered the MYL3 in chondrocytes cell lines, the expression of cartilage degrading enzymes such as MMP13 was significantly increased, while the expression of metabolic factors such as SOX9 was significantly decreased. RNA-sequencing results reminded that MYL3 was associated with Notch signaling. These data suggested that MYL3 may be involved in regulating the synthesis and catabolism of articular cartilage, senescence and degeneration, and even the occurrence of OA through Notch signaling. In order to clarify the role of MYL3-Notch signaling in maintaining the cartilage homeostasis and OA, this project plans to construct a mouse and cell model with inducible knock out MYL3 in chondrocyte. Using RNA sequencing and proteomics and other cell and molecular biological techniques to explore the specific mechanism of MYL3-Notch signal in cartilage senescence and OA at the global, cellular and molecular levels. The aim of this project is to provide a new perspective for cartilage biology and a new potential target for the prevention and treatment of OA.