骨关节炎及创伤等导致的软骨损伤是一种常见而棘手的临床问题。软骨基质积累及软骨细胞分化是损伤软骨再生的重要过程。实验发现，肿瘤坏死因子（TNFα）及其受体（TNFR）组成的信号系统在软骨相关疾病中发挥重要作用。生长因子progranulin（PGRN）是一种多功能生长因子，与TNFα-TNFR信号系统密切相关。在软骨退变等过程中，PGRN通过影响TNFα-TNFR信号系统改善软骨代谢，保护软骨结构。本课题拟通过细胞培养及动物软骨缺损模型建立，明确PGRN重组蛋白使用对于软骨组织再生重建的重要功能。同时，使用体外实验，检测PGRN促进间充质干细胞向软骨细胞分化的相关作用。阐明PGRN通过影响TNFα-TNFR信号系统实现再生相关通路的激活，软骨胞外基质的有效积累及软骨细胞方向的分化的重要功能，从而为进一步了解软骨再生的发生机制提供新的线索。

Cartilage Injury is a common and tough problem in clinic. Accumulation of cartilage matrix and chondrocyte differentiation are proved to be critical process during cartilagenous diseases. It is known that TNFα and TNFα receptors play a critical role in cartilage repair. Progranulin (PGRN) is a multifunctional growth factor which is closely associated with TNFα-TNFR signaling. We have reported that PGRN improves cartilage metabolism and protects against cartilage degeneration through interplay with TNFα-TNFR signaling. Based on the previous reports and our studies, we speculate that PGRN may play a potential role in cartilage regeneration process. To test this hypothesis, we plan to culture mesenchymal stem cells and establish cartilage defect model to investigate the function of PGRN in cartilage differentiation and repair. Moreover, we will use in vitro experiments to assess the effect of PGRN in chondrocyte differentiation. Furthermore, we will illustrate the interplay between PGRN and TNFα-TNFR signaling, which consequently activates the downstream pathways and promotes accumulation of extracellular matrix. The result of this study will shed a light on the mechanism for cartilage repair and provide a potential therapeutic instrument of cartilage injury.