Shu Hengxiang, Gao Yan, Zhang Qin, Sun Haobo, Wang Huazheng, Jing Chengnan, Liu Peng, Geng Dechun, Shen Hao, Gan Minfeng
Department of Orthopaedic Surgery, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou, 215000, Jiangsu, China.
Department of Orthopaedic Surgery, Soochow BenQ Medical Center, Suzhou, 215000, Jiangsu, China.
J Orthop Translat. 2025 Jun 19;53:126-137. doi: 10.1016/j.jot.2025.06.007. eCollection 2025 Jul.
Intervertebral disc degeneration (IVDD), which is known as a common global health concern, has been a significant factor in neck and back pain. The intervertebral discs are avascular structures consisting of the nucleus pulposus, annulus fibrosus, and cartilage endplate, which are crucial for regulating the spinal motion, withstanding stress, and buffering vibration. Due to their special anatomical structure and functional role, they are highly susceptible to stimulation by external factors. Ion channels are transmembrane proteins which have attracted significant attention and great progress in cardiovascular diseases and neurological diseases, and the importance of them in the pathophysiology of IVDD is gaining recognition. They function as a receptor to stimulate the influx of calcium within cells, which acts as a second messenger to activate downstream pathways and upregulate the expression of transcriptional protein, thereby triggering IVDD. This review classified the ion channel families into three types based on their primary activation mechanisms, and then described the regulation of ion channels from transcription and translation to trafficking and expression. Subsequently, the function of ion channels in the pathophysiology of IVDD as well as their potential and practicality in treatment were the main topics of this review. We hope this review could help understand and develop new, specific therapies for IVDD.
Targeted therapeutic strategies for ion channels are particularly critical in the treatment of IVDD. Ion channel-targeted drugs and tissue engineering strategies for ion channels have emerged as novel therapeutic targets for intervening in IVDD by modulating calcium homeostasis, inflammatory responses, and extracellular matrix metabolism in disc cells. In addition, as the development of nanotechnology, the integration of ion channel-targeted therapies with advanced drug delivery systems represents a promising frontier in the treatment of IVDD. Nanoparticle-based carriers and hydrogel-mediated sustained-release platforms have emerged as complementary strategies to enhance drug bioavailability and spatiotemporal control within the avascular, mechanically stressed intervertebral disc microenvironment. Furthermore, systematic exploration of combination therapies integrating ion channel-targeted drugs with complementary pharmacological agents like anti-inflammatory drugs and growth factors warrants rigorous investigation to enhance therapeutic efficacy in IVDD management.
椎间盘退变（IVDD）是一个全球普遍关注的健康问题，是颈痛和背痛的一个重要因素。椎间盘是无血管结构，由髓核、纤维环和软骨终板组成，这些结构对于调节脊柱运动、承受压力和缓冲振动至关重要。由于其特殊的解剖结构和功能作用，它们极易受到外部因素的刺激。离子通道是跨膜蛋白，在心血管疾病和神经疾病中已引起了广泛关注并取得了重大进展，其在IVDD病理生理学中的重要性也日益得到认可。它们作为受体刺激细胞内钙的流入，钙作为第二信使激活下游途径并上调转录蛋白的表达，从而引发IVDD。本综述根据离子通道的主要激活机制将其分为三种类型，然后描述了离子通道从转录、翻译到运输和表达的调控。随后，离子通道在IVDD病理生理学中的功能以及它们在治疗中的潜力和实用性是本综述的主要主题。我们希望本综述有助于理解并开发针对IVDD的新的特异性疗法。
针对离子通道的靶向治疗策略在IVDD治疗中尤为关键。针对离子通道的药物和离子通道组织工程策略已成为通过调节椎间盘细胞内钙稳态、炎症反应和细胞外基质代谢来干预IVDD的新型治疗靶点。此外，随着纳米技术的发展，将离子通道靶向治疗与先进药物递送系统相结合代表了IVDD治疗的一个有前景的前沿领域。基于纳米颗粒的载体和水凝胶介导的缓释平台已成为增强无血管、机械应力作用的椎间盘微环境内药物生物利用度和时空控制的补充策略。此外，系统探索将离子通道靶向药物与抗炎药物和生长因子等互补药理剂相结合的联合疗法，对于提高IVDD治疗效果进行严格研究是必要的。
