title: Oscillating fluid flow activation of gap junction hemichannels induces ATP release from MLO-Y4 osteocytes.
abstract: Mechanical loads are required for optimal bone mass. One mechanism whereby mechanical loads are transduced into localized cellular signals is strain-induced fluid flow through lacunae and canaliculi of bone. Gap junctions (GJs) between osteocytes and osteoblasts provides a mechanism whereby flow-induced signals are detected by osteocytes and transduced to osteoblasts. We have demonstrated the importance of GJ and gap junctional intercellular communication (GJIC) in intracellular calcium and prostaglandin E(2) (PGE(2)) increases in response to flow. Unapposed connexons, or hemichannels, are themselves functional and may constitute a novel mechanotransduction mechanism. Using MC3T3-E1 osteoblasts and MLO-Y4 osteocytes, we examined the time course and mechanism of hemichannel activation in response to fluid flow, the composition of the hemichannels, and the role of hemichannels in flow-induced ATP release. We demonstrate that fluid flow activates hemichannels in MLO-Y4, but not MC3T3-E1, through a mechanism involving protein kinase C, which induces ATP and PGE(2) release.
authors.affiliation: Department of Orthopaedic Surgery, University of California at Davis, Sacramento, California, USA.
authors.forename: Damian C
authors.initials: DC
authors.lastname: Genetos
authors.forename: Curtis J
authors.initials: CJ
authors.lastname: Kephart
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Clare E
authors.initials: CE
authors.lastname: Yellowley
authors.forename: Henry J
authors.initials: HJ
authors.lastname: Donahue
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D018031:Connexin 43 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D051379:Mice; D010011:Osteocytes / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2 / Q000378:metabolism
chemical_list: D018031:Connexin 43; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D015232:Dinoprostone