骨关节炎是中老年人失去活动能力最常见的骨科疾病之一。尽管骨关节炎的发病机制尚不明确，但是软骨基质的降解与软骨细胞的异常肥大被认为是骨关节炎常见的病理变化和最主要的致病机制。我们前期的研究数据表明，骨关节炎患者关节软骨中EGR1有着异常的高表达。而在小鼠骨关节自然退变过程（2月、6月、12月）与骨关节炎造模中，EGR1基因的表达与软骨细胞肥大呈现正相关的关系。我们发现IL-1刺激下，能诱导软骨细胞EGR1的表达。而EGR1/KLF5的抑制剂ML264能够明显抑制IL-1介导的软骨基质的降解。体内实验表明，ML264能够显著抑制小鼠关节炎的关节软骨基质的降解。本项目将通过细胞学、分子生物学等手段，应用EGR1敲除小鼠，探讨EGR1在软骨细胞基质降解与软骨细胞异常肥大中的双重作用。为缓解骨关节炎病理进展及明确其发病机制提供理论依据。

Osteoarthritis is one of the most common orthopedic diseases in which elderly people lose their mobility. Although the pathogenesis of osteoarthritis remains unclear, the degradation of cartilage matrix and the abnormal hypertrophy of chondrocytes are considered as common pathological changes and the most important pathogenic mechanisms of osteoarthritis. Our previous data suggest that EGR1 is abnormally highly expressed in articular cartilage of patients with osteoarthritis. In the natural degeneration process of bone and joint in mice (February, June and December) and osteoarthritis model, EGR1 gene expression and chondrocyte hypertrophy showed a positive correlation. We found that stimulation of IL-1 induced the expression of EGR1 in chondrocytes. While ML264, an inhibitor of EGR1 / KLF5, significantly inhibited IL-1-mediated degradation of the cartilage matrix. In vivo experiments showed that ML264 can significantly protect the mouse joint from degradation of the articular cartilage matrix. The project will use cytology, molecular biology and other means, the use of EGR1 knockout mice to to investigate the dual role of EGR1 in the degradation of chondrocytes and the abnormal hypertrophy of chondrocytes. This project provides a theoretical basis for alleviating the pathological progress of osteoarthritis and clarifying its pathogenesis