Focal activation and intercellular signaling in osteocyte networks initiated by a novel Stokesian Fluid Stimulus Probe (SFSP)
Item
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Title
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Focal activation and intercellular signaling in osteocyte networks initiated by a novel Stokesian Fluid Stimulus Probe (SFSP)
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Identifier
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d_2009_2013:d64e7d679ce2:11472
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identifier
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11919
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Creator
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Wu, Danielle Nicole,
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Contributor
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Sheldon Weinbaum
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Date
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2012
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biomedical engineering | electrophysiology | force probe | gap junction | integrin | mechanotransduction | osteocyte
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Abstract
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Osteocytes are largely distinguished in bone tissue by their dendritic morphology and located in a dynamic cellular labyrinth called the lacunar-canalicular system (LCS). The LCS is surrounded by mineralized matrix that gives bone its unique properties of strength and rigidity and is the major porosity associated with osteocytic stimulation. Osteocytes are a major mechanosensory cell population in bone, but how they communicate within their cellular network and with other cell types under physiological loading conditions require further exploration. Theoretical models have predicted whole bone tissue strains of 0.04-0.3% to be amplified by 1-2 orders of magnitude near regions of loose and rigid attachment of the osteocyte cell process to the canalicular wall. Osteocyte stimulation is widely believed to be linked with load induced bone fluid flow in the pericellular space surrounding osteocytes in the LCS. Mechanisms of osteocyte activation have been explored using fluid flow culture systems, but it is realized that osteocytes have focal regions of mechanotransduction in its 3D microenvironment your in vivo, which uniform flow patterns do not mimic. To achieve focal stimulation we developed a new force probe, the Stokesian fluid stimulus probe (SFSP), for preferential delivery of quantifiable pN-level hydrodynamic forces to mimic forces predicted to occur in vivo. The hydrodynamic disturbance produced a short lived constant strength pressure pulse that propagates nearly instantaneously through the medium creating a nearly spherical expanding fluid bolus that is closely modeled by quasi-steady Stokes flow through a circular orifice in a zero thickness planar wall. Electrophysiological techniques of high temporal and spatial resolution were used to investigate changes in membrane conductance during SFSP stimulation. Forces applied to cell process attachment sites between 1.0 and 2.3 pN initiated cell signaling, and led to responses that were 300 times the average electrical charge and 7 times the average peak conductance of responses produced by cell body stimulation thereby demonstrating osteocyte polarity in signaling initiation. MLO-Y4 cells also demonstrated intercellular signaling directly through gap junctions and indirectly via purinergic nucleotide receptors. These results indicate that direct as well as indirect intercellular signaling are not mutually exclusive events and do occur in parallel.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Engineering
