Tang Pan, Liu Bo
Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, China.
Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine, China.
Heliyon. 2024 Aug 24;10(17):e36905. doi: 10.1016/j.heliyon.2024.e36905. eCollection 2024 Sep 15.
Intervertebral disc herniation, a prevalent condition in spinal surgery that frequently results in low back pain and lower limb dysfunction, significantly impacting patients' quality of life. Several factors, including spine biomechanics, biology, nutrition, injury, and abnormal inflammatory responses, have been associated with the development of intervertebral disc herniation. Among these factors, abnormal inflammatory responses have received considerable attention as a crucial mediator of both clinical symptoms and disease progression during the intervertebral disc herniation process. However, the underlying mechanisms of inflammation-induced intervertebral disc herniation remain inadequately explored. The NF-κB (Nuclear Factor-κB) pathway plays a central role in regulating the expression of proinflammatory cytokines. Research on intervertebral disc herniation has suggested that NF-κB can activate the NLRP3 inflammasome, thereby exacerbating intervertebral disc degeneration. Targeting the NF-κB pathway has shown promise in alleviating disc degeneration and associated pain. Previous research indicated that the upregulation of the NF-κB pathway, achieved through the inhibition of A20 (zinc finger protein A20), accelerated intervertebral disc herniation. In the present study, we observed that increased activation of NF-κB pathway activation suppressed the glycolysis process in nucleus pulposus cells (NPCs), leading to NPC apoptosis. Conversely, inhibition of the NF-κB pathway overactivated promoted the restoration of glycolysis and reversed NPC apoptosis, especially when treated with Lipopolysaccharide (LPS).
椎间盘突出是脊柱外科的一种常见病症，常导致腰背痛和下肢功能障碍，严重影响患者的生活质量。包括脊柱生物力学、生物学、营养、损伤和异常炎症反应在内的多种因素与椎间盘突出的发生发展相关。在这些因素中，异常炎症反应作为椎间盘突出过程中临床症状和疾病进展的关键介质受到了广泛关注。然而，炎症诱导椎间盘突出的潜在机制仍未得到充分探索。核因子-κB（NF-κB）通路在调节促炎细胞因子的表达中起核心作用。对椎间盘突出的研究表明，NF-κB可激活NLRP3炎性小体，从而加剧椎间盘退变。靶向NF-κB通路在减轻椎间盘退变及相关疼痛方面显示出前景。先前的研究表明，通过抑制A20（锌指蛋白A20）实现的NF-κB通路上调加速了椎间盘突出。在本研究中，我们观察到NF-κB通路激活增加会抑制髓核细胞（NPC）的糖酵解过程，导致NPC凋亡。相反，抑制NF-κB通路过度激活可促进糖酵解恢复并逆转NPC凋亡，尤其是在用脂多糖（LPS）处理时。
