Chen Shunlun, Huang Yuming, Lei Linchuan, Yang Cheng, Ran Dongcheng, Zhou Enyu, Wang Hua, Ning Xu
Department of Orthopaedics, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, PR China.
Department of Spinal Surgery, First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, PR China.
Int Immunopharmacol. 2025 Jan 3;145:113785. doi: 10.1016/j.intimp.2024.113785. Epub 2024 Dec 12.
Intervertebral disc degeneration (IVDD) is the primary cause of low back pain (LBP). Enhanced inflammation and reactive oxygen species (ROS) levels can cause apoptosis, which is one of the initial factors of IVDD. Our previous study showed that daphnetin (DAP) alleviates IVDD; however, the underlying mechanisms remain unknown. An IVDD mouse model was established by lumbar disc puncture to investigate the mechanisms of DAP regulation, and DAP was injected intraperitoneally. Moreover, nucleus pulposus cells (NPCs) were challenged with tumor necrosis factor-alpha (TNF-α)/HO to mimic IVDD. Additionally, NPC apoptosis, ROS, and the expression of proinflammatory cytokines were comprehensively assessed. We found that DAP can reverse HO-induced ROS and play an anti-inflammatory role by inhibiting Nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, we found that DAP inhibits the apoptosis of NPCs induced by HO/TNF-α. DAP may regulate ROS production and apoptosis via the Kelch-like ECH-associated protein 1/NF-E2-related factor 2/heme oxygenase-1 (Keap1/Nrf2/HO-1) pathway. These findings were confirmed by in vivo results. The comprehensive nature of our research provides a strong foundation for the potential use of DAP as a therapeutic agent to alleviate IVDD.
椎间盘退变（IVDD）是腰痛（LBP）的主要原因。炎症增强和活性氧（ROS）水平升高可导致细胞凋亡，这是IVDD的初始因素之一。我们之前的研究表明瑞香素（DAP）可减轻IVDD；然而，其潜在机制仍不清楚。通过腰椎间盘穿刺建立IVDD小鼠模型以研究DAP的调控机制，并腹腔注射DAP。此外，用肿瘤坏死因子-α（TNF-α）/血红素加氧酶（HO）刺激髓核细胞（NPCs）以模拟IVDD。另外，全面评估NPC凋亡、ROS及促炎细胞因子的表达。我们发现DAP可逆转HO诱导的ROS，并通过抑制核因子-κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）途径发挥抗炎作用。此外，我们发现DAP可抑制HO/TNF-α诱导的NPC凋亡。DAP可能通过kelch样ECH相关蛋白1/核因子E2相关因子2/血红素加氧酶-1（Keap1/Nrf2/HO-1）途径调节ROS产生和细胞凋亡。体内结果证实了这些发现。我们研究的全面性为DAP作为缓解IVDD的治疗药物的潜在应用提供了坚实基础。
