title: Mechanosensitivity of bone cells to oscillating fluid flow induced shear stress may be modulated by chemotransport.
abstract: Fluid flow has been shown to be a potent physical stimulus in the regulation of bone cell metabolism. In addition to membrane shear stress, loading-induced fluid flow will enhance chemotransport due to convection or mass transport thereby affecting the biochemical environment surrounding the cell. This study investigated the role of oscillating fluid flow induced shear stress and chemotransport in cellular mechanotransduction mechanisms in bone. Intracellular calcium mobilization and prostaglandin E(2) (PGE(2)) production were studied with varying levels of shear stress and chemotransport. In this study MC3T3-E1 cells responded to oscillating fluid flow with both an increase in intracellular calcium concentration ([Ca(2+)](i)) and an increase in PGE(2) production. These fluid flow induced responses were modulated by chemotransport. The percentage of cells responding with an [Ca(2+)](i) oscillation increased with increasing flow rate, as did the production of PGE(2). In addition, depriving the cells of nutrients during fluid flow resulted in an inhibition of both [Ca(2+)](i) mobilization and PGE(2) production. These data suggest that depriving the cells of a yet to be determined biochemical factor in media affects the responsiveness of bone cells even at a constant peak shear stress. Chemotransport alone will not elicit a response, but it appears that sufficient nutrient supply or waste removal is needed for the response to oscillating fluid flow induced shear stress.
authors.affiliation: Musculoskeletal Research Laboratory, Department of Orthopaedics, Pennsylvania State University, College of Medicine, 17033, Hershey, PA, USA. thdonahu@mtu.edu
authors.forename: T L Haut
authors.initials: TL
authors.lastname: Donahue
authors.forename: T R
authors.initials: TR
authors.lastname: Haut
authors.forename: C E
authors.initials: CE
authors.lastname: Yellowley
authors.forename: H J
authors.initials: HJ
authors.lastname: Donahue
authors.forename: C R
authors.initials: CR
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D045744:Cell Line, Tumor; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007424:Intracellular Fluid / Q000378:metabolism*; D007552:Isotonic Solutions / Q000494:pharmacology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D009994:Osmolar Concentration; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D002121:Calcium Channel Blockers; D016895:Culture Media, Serum-Free; C072670:Hanks Balanced Salt Solution; D007552:Isotonic Solutions; D015232:Dinoprostone; D002118:Calcium