Zhao Jiangminghao, Xu Peichuan, Li Tao, Yuan Jinghong, Zhao Wenrui, Ding Rui, Yang Guoyu, Xie Jiajun, Huang Guanfeng, Peng Zhidong, Miao Xinxin, Cheng Xigao
Department of Orthopaedics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Jiangxi Provincial Key Laboratory of Spine and Spinal Cord Disease, Nanchang University, Nanchang, China.
Mater Today Bio. 2025 Jun 28;33:102027. doi: 10.1016/j.mtbio.2025.102027. eCollection 2025 Aug.
Intervertebral disc degeneration (IVDD) is recognized as a significant underlying factor contributing to clinical neck and low back pain. The cartilaginous endplates (CEP) serve as a selectively permeable barrier, which is essential for maintaining the internal homeostasis of the intervertebral disc (IVD). Dysfunction of the CEP is closely related to the initiation and progression of IVDD. In this paper, we demonstrate that CCAAT enhancer-binding protein () is crucial for the degeneration of the CEP. We observed a significant downregulation of in CEP degeneration. The deficiency of leads to inflammation, degradation of the extracellular matrix (ECM), and calcification of endplate chondrocytes (EPCs). Conversely, overexpression of mitigates these detrimental processes. Mechanistically, deficiency down-regulates the transcription level of lactoferrin (), which in turn activates the JAK2/STAT3 inflammatory signaling pathway, and STAT3 inhibits the transcription of . These findings unveil a previously unidentified positive feedback loop, CEBPE-LTF-STAT3, that modulates EPCs degeneration. Importantly, a lipid nanoparticle targeting chondrocytes for the efficient delivery of a -overexpressing plasmid significantly reduced ECM degradation and the calcification process in CEP, substantially attenuating the progression of IVDD. This highlights promising targets and effective strategies for mitigating the impact of IVDD.
椎间盘退变（IVDD）被认为是导致临床颈部和下背部疼痛的一个重要潜在因素。软骨终板（CEP）作为一种选择性渗透屏障，对于维持椎间盘（IVD）的内部稳态至关重要。CEP功能障碍与IVDD的发生和发展密切相关。在本文中，我们证明CCAAT增强子结合蛋白（）对于CEP退变至关重要。我们观察到在CEP退变过程中显著下调。的缺乏导致炎症、细胞外基质（ECM）降解以及终板软骨细胞（EPC）钙化。相反，的过表达减轻了这些有害过程。机制上，缺乏下调乳铁蛋白（）的转录水平，进而激活JAK2/STAT3炎症信号通路，并且STAT3抑制的转录。这些发现揭示了一个先前未被识别的正反馈回路，即CEBPE-LTF-STAT3，它调节EPC退变。重要的是，一种靶向软骨细胞以有效递送过表达质粒的脂质纳米颗粒显著减少了CEP中的ECM降解和钙化过程，大大减轻了IVDD的进展。这突出了减轻IVDD影响的有前景的靶点和有效策略。
