瞬时受体电位通道在关节疾病中的作用。
The role of transient receptor potential channels in joint diseases.
机构信息
ETH Zurich, Hoenggerbergring 64, 8093 Zurich,
出版信息
Eur Cell Mater. 2017 Oct 10;34:180-201. doi: 10.22203/eCM.v034a12.
Transient receptor potential channels (TRP channels) are cation selective transmembrane receptors with diverse structures, activation mechanisms and physiological functions. TRP channels act as cellular sensors for a plethora of stimuli, including temperature, membrane voltage, oxidative stress, mechanical stimuli, pH and endogenous, as well as, exogenous ligands, thereby illustrating their versatility. As such, TRP channels regulate various functions in both excitable and non-excitable cells, mainly by mediating Ca2+ homeostasis. Dysregulation of TRP channels is implicated in many pathologies, including cardiovascular diseases, muscular dystrophies and hyperalgesia. However, the importance of TRP channel expression, physiological function and regulation in chondrocytes and intervertebral disc (IVD) cells is largely unexplored. Osteoarthritis (OA) and degenerative disc disease (DDD) are chronic age-related disorders that significantly affect the quality of life by causing pain, activity limitation and disability. Furthermore, currently available therapies cannot effectively slow-down or stop progression of these diseases. Both OA and DDD are characterised by reduced tissue cellularity, enhanced inflammatory responses and molecular, structural and mechanical alterations of the extracellular matrix, hence affecting load distribution and reducing joint flexibility. However, knowledge on how chondrocytes and IVD cells sense their microenvironment and respond to its changes is still limited. In this review, we introduced six families of mammalian TRP channels, their mechanisms of activation, as well as, activation-driven cellular consequences. We summarised the current knowledge on TRP channel expression and activity in chondrocytes and IVD cells, as well as, the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.
瞬时受体电位通道(TRP 通道)是阳离子选择性跨膜受体,具有多种结构、激活机制和生理功能。TRP 通道作为细胞传感器,对多种刺激物(包括温度、膜电压、氧化应激、机械刺激、pH 值以及内源性和外源性配体)敏感,从而体现了其多功能性。因此,TRP 通道调节兴奋和非兴奋细胞的各种功能,主要通过调节 Ca2+稳态。TRP 通道的失调与许多病理学有关,包括心血管疾病、肌肉营养不良和痛觉过敏。然而,TRP 通道在软骨细胞和椎间盘(IVD)细胞中的表达、生理功能和调节的重要性在很大程度上尚未得到探索。骨关节炎(OA)和退行性椎间盘疾病(DDD)是慢性与年龄相关的疾病,通过引起疼痛、活动受限和残疾,显著影响生活质量。此外,目前可用的治疗方法无法有效减缓或阻止这些疾病的进展。OA 和 DDD 的特征是组织细胞减少、炎症反应增强以及细胞外基质的分子、结构和机械改变,从而影响负荷分布并降低关节灵活性。然而,关于软骨细胞和 IVD 细胞如何感知其微环境以及对其变化做出反应的知识仍然有限。在这篇综述中,我们介绍了哺乳动物 TRP 通道的六个家族、它们的激活机制以及激活驱动的细胞后果。我们总结了 TRP 通道在软骨细胞和 IVD 细胞中的表达和活性的现有知识,以及 TRP 通道作为治疗 OA 和 DDD 的治疗靶点的重要性。