Department of Bone and Joint Surgery, Institute of Orthopedic Diseases, The First Afliated Hospital, Jinan University, Guangzhou 510630, Guangdong Province, PR China; Department of Orthopedics, Changsha Hospital of Hunan Normal University, Changsha 410006, Hunan Province, PR China.
Department of Orthopedics, Changsha Hospital of Hunan Normal University, Changsha 410006, Hunan Province, PR China.
Cytokine. 2023 May;165:156168. doi: 10.1016/j.cyto.2023.156168. Epub 2023 Mar 22.
Osteoarthritis (OA) is the most common joint disease which can lead to serious disability. Interferon regulatory factor 7 (IRF7) is a member of the interferon regulatory factor family. This study aimed to explore the function and potential mechanism of IRF7 in OA. Our results found that IRF7 was increased in LPS-stimulated C28/I2 chondrocytes and in OA mice established with medial menisco-tibial ligament (MMTL) transection. IRF7 silencing enhanced cell viability, reduced IL-18 and IL-1β levels and suppressed cell apoptosis. IRF7 knockdown decreased ROS and LDH levels, and inhibited pyroptosis in LPS-treated chondrocytes. IRF7 negatively regulated FGF21 expression. FGF21 overexpression alleviated pyroptosis in LPS-stimulated chondrocytes. Knockdown of IRF7 improved OA injury in mice. In conclusion, our study demonstrates that silencing of IRF7 alleviates OA by inhibiting chondrocyte pyroptosis via upregulation of FGF21.
骨关节炎（OA）是最常见的关节疾病，可导致严重残疾。干扰素调节因子 7（IRF7）是干扰素调节因子家族的一员。本研究旨在探讨 IRF7 在 OA 中的功能和潜在机制。我们的结果发现，IRF7 在 LPS 刺激的 C28/I2 软骨细胞和内侧半月板胫骨韧带（MMTL）横断建立的 OA 小鼠中增加。IRF7 沉默增强细胞活力，降低 IL-18 和 IL-1β水平，并抑制细胞凋亡。IRF7 敲低降低了 ROS 和 LDH 水平，并抑制 LPS 处理的软骨细胞中的细胞焦亡。IRF7 负调控 FGF21 的表达。FGF21 的过表达减轻了 LPS 刺激的软骨细胞中的细胞焦亡。IRF7 的敲低改善了小鼠的 OA 损伤。总之，本研究表明，沉默 IRF7 通过上调 FGF21 抑制软骨细胞焦亡来减轻 OA。
