Department of Orthopedic Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Membr Biol. 2012 Jul;245(7):401-9. doi: 10.1007/s00232-012-9462-2. Epub 2012 Jul 15.
Osteoblasts sense and respond to mechanical stimuli in a process involving influx and release of large ions and signaling molecules. Unapposed gap junction hemichannels formed of connexin43 (Cx43) have been proposed as a major route for such exchange, in particular for release of ATP and prostaglandin E₂ (PGE₂) in osteocytes. However, we have found that Cx43-null osteoblasts have unaltered, mechanically induced PGE₂ release and ATP-induced YoPro dye uptake. In contrast, PGE₂ release in response to fluid shear stress is abolished in P2X₇ receptor (P2X₇R)-null osteoblasts, and ATP-induced dye uptake is attenuated following treatment of wild-type cells with a P2X₇R or Pannexin1 (Panx1) channel blocker. These data indicate that Panx1 channels, in concert with P2X₇R, likely form a molecular complex that performs the hemichannel function in osteoblast mechanosignaling.
成骨细胞通过离子和信号分子的内流和释放来感知和响应机械刺激。缝隙连接半通道由连接蛋白 43（Cx43）组成，被认为是这种交换的主要途径，特别是在成骨细胞中释放 ATP 和前列腺素 E₂（PGE₂）。然而，我们发现 Cx43 基因敲除的成骨细胞的机械诱导的 PGE₂释放和 ATP 诱导的 YoPro 染料摄取没有改变。相比之下，在 P2X7 受体（P2X7R）基因敲除的成骨细胞中，流体切应力引起的 PGE₂释放被消除，而在用 P2X7R 或 Pannexin1（Panx1）通道阻滞剂处理野生型细胞后，ATP 诱导的染料摄取被减弱。这些数据表明，Panx1 通道与 P2X7R 一起可能形成一个分子复合物，在成骨细胞机械信号转导中发挥半通道功能。
