Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling

作者：Qunbo Meng, Kaiwen Liu, Zhenchuan Liu, Jinbo Liu, Ziyu Tian, Shanshan Qin, Jianlu Wei, Lei Cheng · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1251517 · 被引用次数：22 · 研究领域：Spine and Intervertebral Disc Pathology、Pain Mechanisms and Treatments、Musculoskeletal pain and rehabilitation

Background Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects. Objective This study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein. Methods We exploited a rat needle model to investigate digoxin’s role in intervertebral disc degeneration in vivo . Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro . Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin. Results Digoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc...