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Joint diseases: from connexins to gap junctions.
Nature Reviews Rheumatology ( IF 29.4 ) Pub Date : 2017-12-19 , DOI: 10.1038/nrrheum.2017.204
Henry J Donahue 1 , Roy W Qu 2 , Damian C Genetos 2
Affiliation  

Connexons form the basis of hemichannels and gap junctions. They are composed of six tetraspan proteins called connexins. Connexons can function as individual hemichannels, releasing cytosolic factors (such as ATP) into the pericellular environment. Alternatively, two hemichannel connexons from neighbouring cells can come together to form gap junctions, membrane-spanning channels that facilitate cell-cell communication by enabling signalling molecules of approximately 1 kDa to pass from one cell to an adjacent cell. Connexins are expressed in joint tissues including bone, cartilage, skeletal muscle and the synovium. Indicative of their importance as gap junction components, connexins are also known as gap junction proteins, but individual connexin proteins are gaining recognition for their channel-independent roles, which include scaffolding and signalling functions. Considerable evidence indicates that connexons contribute to the function of bone and muscle, but less is known about the function of connexons in other joint tissues. However, the implication that connexins and gap junctional channels might be involved in joint disease, including age-related bone loss, osteoarthritis and rheumatoid arthritis, emphasizes the need for further research into these areas and highlights the therapeutic potential of connexins.

中文翻译:

关节疾病:从连接蛋白到间隙连接。

连接子形成半通道和间隙连接的基础。它们由六种称为连接蛋白的四跨蛋白组成。连接子可以作为单独的半通道发挥作用,将胞质因子(如 ATP)释放到细胞周环境中。或者,来自相邻细胞的两个半通道连接子可以聚集在一起形成间隙连接,跨膜通道,通过使大约 1 kDa 的信号分子从一个细胞传递到相邻细胞来促进细胞间通讯。连接蛋白在关节组织中表达,包括骨、软骨、骨骼肌和滑膜。连接蛋白也被称为间隙连接蛋白,表明它们作为间隙连接组件的重要性,但单个连接蛋白因其独立于通道的作用而获得认可,其中包括脚手架和信号功能。相当多的证据表明连接子有助于骨骼和肌肉的功能,但对连接子在其他关节组织中的功能知之甚少。然而,连接蛋白和间隙连接通道可能与关节疾病有关,包括与年龄相关的骨质流失、骨关节炎和类风湿性关节炎,这表明需要对这些领域进行进一步研究,并强调连接蛋白的治疗潜力。
更新日期:2017-12-19
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