关节软骨损伤与退变是骨关节炎(OA)出现的最直接原因。我们前期研究发现(81171697)：与正常小鼠OA相比，PGRN-/-敲除小鼠OA表现出关节软骨的加速退变和损伤；在OA发生过程中，关节软骨损伤会诱导ER stress并激活UPR，UPR激活依赖于PGRN，作为UPR重要分子XBP1及核心通路IRE1/XBP1如何参与OA发生及在OA关节软骨损伤中的作用与机制都不清楚。本研究综合运用XBP1条件性敲除(cKO)小鼠和XBP1 转基因(Tg)小鼠等不同类型小鼠构建OA模型，结合体外趾骨组织团块培养、IHC、Q-PCR、免疫印迹等实验方法，检测XBP1在OA关节软骨损伤中的作用与功能；阐明XBP1调节OA发生与PGRN信号通路、炎性因子TNFa及下游NF-κB信号通路的关系；揭示XBP1介导UPR信号通路调控OA关节软骨损伤与OA发生的作用与机制，为探索和解析新的炎症调控机制奠定基础。

Damage and degeneration of articular cartilage are the most direct causes of osteoarthritis (OA).Our previous study (81171697) showed that the OA of PGRN-/- mice exhibited accelerated degeneration and injury of articular cartilage compared with the OA of wild type (WT). The articular cartilage damage will induce ER stress and activate UPR, and the activation of UPR is dependent on PGRN. However, it remains unknown that how to regulate OA occurrence with the UPR important molecule XBP1 and IRE1/XBP1 core signal pathway, its function and mechanism during the injury of OA articular cartilage are also unknown. In this study, we constructed OA mice model with XBP1 conditional knockout (cKO) mice and XBP1 transgenetic (Tg) mice. The models, combined with such methods as mouse metatarsal bones induced culture in vitro, immunohistochemistry (IHC) ,Q-PCR and immunoblotting, detected the function of XBP1 during OA articular cartilage injury, clarified the relationship between OA occurrence modulated by XBP1 and PGRN signal pathway, inflammatory factor TNFa and downstream NF-κB signal pathway, revealed the effect and mechanism of XBP1-mediated UPR signal pathway during the injury of OA articular cartilage and OA occurrence. This study lays the foundation for exploring and parsing the new regulatory mechanisms of inflammation.