Institute for Biomechanics, D-HEST, ETH Zurich, Hönggerbergring 64, HPP-O12, 8093 Zurich,
Eur Cell Mater. 2018 Nov 19;36:231-250. doi: 10.22203/eCM.v036a17.
Intervertebral disc (IVD) cells are naturally exposed to high osmolarity and complex mechanical loading, which drive microenvironmental osmotic changes. Age- and degeneration-induced degradation of the IVD's extracellular matrix causes osmotic imbalance, which, together with an altered function of cellular receptors and signalling pathways, instigates local osmotic stress. Cellular responses to osmotic stress include osmoadaptation and activation of pro-inflammatory pathways. This review summarises the current knowledge on how IVD cells sense local osmotic changes and translate these signals into physiological or pathophysiological responses, with a focus on inflammation. Furthermore, it discusses the expression and function of putative membrane osmosensors (e.g. solute carrier transporters, transient receptor potential channels, aquaporins and acid-sensing ion channels) and osmosignalling mediators [e.g. tonicity response-element-binding protein/nuclear factor of activated T-cells 5 (TonEBP/NFAT5), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)] in healthy and degenerated IVDs. Finally, an overview of the potential therapeutic targets for modifying osmosensing and osmosignalling in degenerated IVDs is provided.
椎间盘（IVD）细胞自然暴露于高渗透压和复杂的机械加载下，这些因素会导致微环境渗透压发生变化。IVD 细胞外基质的年龄和退化引起的渗透压失衡，以及细胞受体和信号通路功能的改变，引发局部渗透压应激。细胞对渗透压应激的反应包括渗透适应和促炎途径的激活。本综述总结了目前关于 IVD 细胞如何感知局部渗透压变化，并将这些信号转化为生理或病理生理反应的知识，重点讨论了炎症。此外，还讨论了潜在的膜渗透压感受器（例如溶质载体转运蛋白、瞬时受体电位通道、水通道蛋白和酸感应离子通道）和渗透压信号转导介质（例如张力反应元件结合蛋白/激活 T 细胞的核因子 5（TonEBP/NFAT5）、核因子 kappa-轻链增强子的 B 细胞激活（NF-κB））在健康和退变的 IVD 中的表达和功能。最后，提供了用于修饰退变 IVD 中渗透压感知和信号转导的潜在治疗靶点的概述。
