title: Gap junctional communication in osteocytes is amplified by low intensity vibrations in vitro.
abstract: The physical mechanism by which cells sense high-frequency mechanical signals of small magnitude is unknown. During exposure to vibrations, cell populations within a bone are subjected not only to acceleratory motions but also to fluid shear as a result of fluid-cell interactions. We explored displacements of the cell nucleus during exposure to vibrations with a finite element (FE) model and tested in vitro whether vibrations can affect osteocyte communication independent of fluid shear. Osteocyte like MLO-Y4 cells were subjected to vibrations at acceleration magnitudes of 0.15 g and 1 g and frequencies of 30 Hz and 100 Hz. Gap junctional intracellular communication (GJIC) in response to these four individual vibration regimes was investigated. The FE model demonstrated that vibration induced dynamic accelerations caused larger relative nuclear displacement than fluid shear. Across the four regimes, vibrations significantly increased GJIC between osteocytes by 25%. Enhanced GJIC was independent of vibration induced fluid shear; there were no differences in GJIC between the four different vibration regimes even though differences in fluid shear generated by the four regimes varied 23-fold. Vibration induced increases in GJIC were not associated with altered connexin 43 (Cx43) mRNA or protein levels, but were dependent on Akt activation. Combined, the in silico and in vitro experiments suggest that externally applied vibrations caused nuclear motions and that large differences in fluid shear did not influence nuclear motion (<1%) or GJIC, perhaps indicating that vibration induced nuclear motions may directly increase GJIC. Whether the increase in GJIC is instrumental in modulating anabolic and anti-catabolic processes associated with the application of vibrations remains to be determined.
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States of America; Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Gunes
authors.initials: G
authors.lastname: Uzer
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Suphannee
authors.initials: S
authors.lastname: Pongkitwitoon
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Cheng
authors.initials: C
authors.lastname: Ian
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: William R
authors.initials: WR
authors.lastname: Thompson
authors.affiliation: Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Janet
authors.initials: J
authors.lastname: Rubin
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Meilin E
authors.initials: ME
authors.lastname: Chan
authors.affiliation: Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Judex
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D020342:Finite Element Analysis; D005452:Fluoresceins / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D051379:Mice; D010011:Osteocytes / Q000166:cytology* / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D033081:Shear Strength; D015398:Signal Transduction; D014732:Vibration
chemical_list: D005452:Fluoresceins; D051057:Proto-Oncogene Proteins c-akt; C007740:fluorexon