Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin
Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin
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DOI：
10.1091/mbc.e04-10-0912
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发表时间：
2005-07-01
影响因子：
3.3
通讯作者：
Jiang, JX
中科院分区：
文献类型：
--
作者：
Cherian, PP;Siller-Jackson, AJ;Jiang, JX
机械感受性骨细胞表达大量的缝隙连接成分连接蛋白(Cx)43；然而，缝隙连接仅在其树突的小尖端活跃，这表明Cx43还有另一种功能。原代骨细胞和类成骨细胞MLO-Y4细胞均通过释放细胞内前列腺素E-2(PGE(2))来响应流体剪切力。低密度电镀的细胞比高密度电镀的细胞释放更多的PGE(2)。这种反应被Cx43的反义以及缝隙连接和半通道抑制剂18β-甘草次酸和甘草次酸和甘草酮显著降低，即使在没有物理接触的细胞中也是如此，这表明Cx43-半通道参与了这一过程。其他通道的抑制剂，如嘌呤能受体P2X(7)和前列腺素转运体PGT，对PGE(2)的释放没有影响。细胞表面生物素化分析表明，切应力使细胞表面Cx43的表达增加。综上所述，这些结果表明，流体剪切应力诱导Cx43移位到膜表面，Cx43形成的未对位半通道是响应机械应变而释放PGE(2)的新途径。
Mechanosensing bone osteocytes express large amounts of connexin (Cx)43, the component of gap junctions; yet, gap junctions are only active at the small tips of their dendritic processes, suggesting another function for Cx43. Both primary osteocytes and the osteocyte-like MLO-Y4 cells respond to fluid flow shear stress by releasing intracellular prostaglandin E-2 (PGE(2)). Cells plated at lower densities release more PGE(2) than cells plated at higher densities. This response was significantly reduced by antisense to Cx43 and by the gap junction and hemichannel inhibitors 18 beta-glycyrrhetinic acid and carbenoxolone, even in cells without physical contact, suggesting the involvement of Cx43-hemichannels. Inhibitors of other channels, such as the purinergic receptor P2X(7) and the prostaglandin transporter PGT, had no effect on PGE(2) release. Cell surface biotinylation analysis showed that surface expression of Cx43 was increased by shear stress. Together, these results suggest fluid flow shear stress induces the translocation of Cx43 to the membrane surface and that unapposed hemichannels formed by Cx43 serve as a novel portal for the release of PGE(2) in response to mechanical strain.