Abstract
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 E&sub2; (PGE&sub2;) in osteocytes. However, we have found that Cx43-null osteoblasts have unaltered, mechanically induced PGE&sub2; release and ATP-induced YoPro dye uptake. In contrast, PGE&sub2; 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.