Transient receptor potential vanilloid 4: The sixth sense of the musculoskeletal system?

Transient receptor potential vanilloid 4: The sixth sense of the musculoskeletal system?
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DOI:
10.1111/j.1749-6632.2010.05389.x
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发表时间:
2010-03
影响因子:
5.2
通讯作者:
Liedtke W
Liedtke W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Guilak F;Leddy HA;Liedtke W

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过去二十年来,离子通道瞬时受体电位(TRP)超家族的关键发现揭示了细胞感知典型“五种感觉”之外的多种刺激的潜在机制,识别出由热、冷、机械负荷、渗透压和其他物理和化学刺激门控的离子通道。瞬时受体电位香草酸 4 (TRPV4) 是一种 Ca2+ 渗透性非选择性阳离子通道,似乎在多种肌肉骨骼组织中发挥机械或渗透感觉作用。在关节软骨中,TRPV4 表现出渗透敏感性,控制细胞体积恢复和对渗透压的其他生理反应。 TRPV4 在成骨细胞和破骨细胞中表达,TRPV4 的缺失可防止废用性骨质流失。 TRPV4 激活通过诱导 SOX9 转录促进软骨形成,而 TRPV4 功能获得性突变会导致发育性骨骼发育不良,这表明 TRPV4 在骨骼发育中发挥着关键作用。这些研究为感觉通道 TRPV4 在控制肌肉骨骼组织中的调节作用提供了越来越多的证据。
The critical discovery in the past two decades of the Transient Receptor Potential (TRP) superfamily of ion channels has revealed the potential mechanisms by which cells sense diverse stimuli beyond the prototypical “five senses”, identifying ion channels that are gated by heat, cold, mechanical loading, osmolarity, and other physical and chemical stimuli. Transient receptor potential vanilloid 4 (TRPV4) is a Ca2+-permeable non-selective cation channel that appears to play a mechano- or osmosensory roles in several musculoskeletal tissues. In articular cartilage, TRPV4 exhibits osmotic sensitivity, controlling cellular volume recovery and other physiologic responses to osmotic stress. TRPV4 is expressed in both osteoblasts and osteoclasts, and the absence of TRPV4 prevents disuse-induced bone loss. TRPV4 activation promotes chondrogenesis by inducing SOX9 transcription, whereas a TRPV4 gain-of-function mutation leads to a developmental skeletal dysplasia, suggesting a critical role for TRPV4 in skeletal development. These studies provide mounting evidence for a regulatory role for the sensory channel TRPV4 in control of musculoskeletal tissues.
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