Hemichannels formed by connexin 43 play an important role in the release of prostaglandin E2 by osteocytes in response to mechanical strain
Hemichannels formed by connexin 43 play an important role in the release of prostaglandin E2 by osteocytes in response to mechanical strain
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DOI：
10.1080/15419060390262994
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发表时间：
2003-07-01
影响因子：
--
通讯作者：
Cherian, PP
中科院分区：
文献类型：
--
作者：
Jiang, JX;Cherian, PP
骨细胞是嵌入骨基质中的机械感觉细胞，可将应变转化为信号并调节骨重塑。我们之前使用骨细胞样MLO-Y4细胞的研究表明，流体流动剪切应力（FFSS）增加连接蛋白（Cx） 43蛋白表达、前列腺素E-2 （PGE(2)）释放和细胞间偶联，而PGE(2)是FFSS和间隙连接之间的重要介质。然而，Cx43在FFSS反应中pge2释放中的作用尚不清楚。在这里，没有或很少有细胞间通道的装载ffss的MLO-Y4细胞比那些密度更高的细胞释放更多的PGE(2)。反义Cx43寡核苷酸和18 - β -甘草次酸（一种特殊的间隙连接和半通道阻滞剂）在所有细胞密度测试中显著减少了FFSS的PGE(2)释放，特别是在没有间隙连接的最低密度细胞中。FFSS、流体流动培养基和PGE(2)增加了染料摄取活性。此外，FFSS诱导Cx43向细胞表面迁移；该表面表达的Cx43对Triton-X-100的溶解产生了抗性。我们的研究结果表明，Cx43形成的半通道，而不是细胞间通道，可能在响应FFSS的细胞内PGE释放中发挥主导作用(2)。
Osteocytes embedded in the matrix of bone are mechanosensory cells that translate strain into signals and regulate bone remodeling. Our previous studies using osteocyte-like MLO-Y4 cells have shown that fluid flow shear stress (FFSS) increases connexin (Cx) 43 protein expression, prostaglandin E-2 (PGE(2)) release, and intercellular coupling, and PGE(2) is an essential mediator between FFSS and gap junctions. However, the role of Cx43 in the release of PGE 2 in response to FFSS is unknown. Here, the FFSS-loaded MLO-Y4 cells with no or few intercellular channels released significantly more PGE(2) per cell than those cells at higher densities. Antisense Cx43 oligonucleotides and 18 beta-glycyrrhetinic acid, a specific gap junction and hemichannel blocker, significantly reduced PGE(2) release by FFSS at all cell densities tested, especially cells at the lowest density without gap junctions. FFSS, fluid flow-conditioned medium, and PGE(2) increased the activity of dye uptake. Moreover, FFSS induced Cx43 to migrate to the surface of the cell; this surface expressed Cx43 developed resistance to Triton-X-100 solublization. Our results suggest that hemichannels formed by Cx43, instead of intercellular channels, are likely to play a predominant role in the release of intracellular PGE(2) in response to FFSS.