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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Biomech
2014 ; 47
(8
): 1838-45
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Integrative transcriptomic and proteomic analysis of osteocytic cells exposed to
fluid flow reveals novel mechano-sensitive signaling pathways
#MMPMID24720889
Govey PM
; Jacobs JM
; Tilton SC
; Loiselle AE
; Zhang Y
; Freeman WM
; Waters KM
; Karin NJ
; Donahue HJ
J Biomech
2014[Jun]; 47
(8
): 1838-45
PMID24720889
show ga
Osteocytes, positioned within bone?s porous structure, are subject to
interstitial fluid flow upon whole bone loading. Such fluid flow is widely
theorized to be a mechanical signal transduced by osteocytes, initiating a poorly
understood cascade of signaling events mediating bone adaptation to mechanical
load. The objective of this study was to examine the time course of flow-induced
changes in osteocyte gene transcript and protein levels using high-throughput
approaches. Osteocyte-like MLO-Y4 cells were subjected to 2h of oscillating fluid
flow (1Pa peak shear stress) and analyzed following 0, 2, 8, and 24h post-flow
incubation. Transcriptomic microarray analysis, followed by gene ontology pathway
analysis, demonstrated fluid flow regulation of genes consistent with both known
and unknown metabolic and inflammatory responses in bone. Additionally, two of
the more highly up-regulated gene products - chemokines Cxcl1 and Cxcl2,
supported by qPCR - have not previously been reported as responsive to fluid
flow. Proteomic analysis demonstrated greatest up-regulation of the ATP-producing
enzyme NDK, calcium-binding Calcyclin, and G protein-coupled receptor kinase 6.
Finally, an integrative pathway analysis merging fold changes in transcript and
protein levels predicted signaling nodes not directly detected at the sampled
time points, including transcription factors c-Myc, c-Jun, and RelA/NF-?B. These
results extend our knowledge of the osteocytic response to fluid flow, most
notably up-regulation of Cxcl1 and Cxcl2 as possible paracrine agents for
osteoblastic and osteoclastic recruitment. Moreover, these results demonstrate
the utility of integrative, high-throughput approaches in place of a traditional
candidate approach for identifying novel mechano-sensitive signaling molecules.