Journal
JOURNAL OF MEMBRANE BIOLOGY
Volume 245, Issue 7, Pages 401-409Publisher
SPRINGER
DOI: 10.1007/s00232-012-9462-2
Keywords
P2X(7)R; ATP; Osteoblast; Gap junction; Dye uptake
Funding
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease [DK091466, DK081435]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR057139]
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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-2 (PGE(2)) in osteocytes. However, we have found that Cx43-null osteoblasts have unaltered, mechanically induced PGE(2) release and ATP-induced YoPro dye uptake. In contrast, PGE(2) release in response to fluid shear stress is abolished in P2X(7) receptor (P2X(7)R)-null osteoblasts, and ATP-induced dye uptake is attenuated following treatment of wild-type cells with a P2X(7)R or Pannexin1 (Panx1) channel blocker. These data indicate that Panx1 channels, in concert with P2X(7)R, likely form a molecular complex that performs the hemichannel function in osteoblast mechanosignaling.
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