THE ROLE OF TRANSIENT RECEPTOR POTENTIAL CHANNELS IN JOINT DISEASES
THE ROLE OF TRANSIENT RECEPTOR POTENTIAL CHANNELS IN JOINT DISEASES
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DOI：
10.22203/ecm.v034a12
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发表时间：
2017-07-01
影响因子：
3.1
通讯作者：
Wuertz-Kozak, K.
中科院分区：
文献类型：
--
作者：
Krupkova, O.;Zvick, J.;Wuertz-Kozak, K.
瞬时受体电位通道（TRP channels）是一类结构、激活机制和生理功能多样的阳离子选择性跨膜受体。TRP通道作为细胞的传感器的刺激，包括温度，膜电压，氧化应激，机械刺激，pH值和内源性以及外源性配体，从而说明其多功能性。因此，TRP通道主要通过介导Ca2+稳态来调节可兴奋和不可兴奋细胞中的各种功能。TRP通道的失调涉及许多病理学，包括心血管疾病、肌营养不良和痛觉过敏。然而，软骨细胞和椎间盘（IVD）细胞中TRP通道表达、生理功能和调节的重要性在很大程度上未被探索。骨关节炎（OA）和退行性椎间盘疾病（DDD）是慢性年龄相关性疾病，通过引起疼痛、活动受限和残疾而显著影响生活质量。此外，目前可用的疗法不能有效地减缓或阻止这些疾病的进展。OA和DDD的特征都是组织细胞减少，炎症反应增强以及细胞外基质的分子、结构和机械改变，因此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并对其变化做出反应的知识仍然有限。本文介绍了哺乳动物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。我们总结了软骨细胞和IVD细胞中TRP通道表达和活性的现有知识，以及TRP通道作为治疗OA和DDD的治疗靶点的意义。
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 and the significance of TRP channels as therapeutic targets for the treatment of OA and DDD.