Novel early response genes in osteoblasts exposed to dynamic fluid flow

Giridhar M. Shivaram, Chi Hyun Kim, Nikhil N. Batra, Wuchen Yang, Stephen E. Harris, Christopher R. Jacobs

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Cyclic mechanical loads applied to the skeleton from habitual physical activity result in increased bone formation. These loads lead to dynamic pressure gradients and oscillatory flow of bone interstitial fluid, which, in turn, exposes cells resident in the bony matrix to oscillatory fluid shear stress. Dynamic fluid flow has previously been shown to be a potent anabolic stimulus for cultured osteoblasts. In this study, we used cDNA microarrays to examine early phase, broad-spectrum gene expression in MC3T3-E1 osteoblasts in response to physical stimulation. RNA was harvested at 30min and 1h post-stimulation. RNA was used for microarray hybridization as well as subsequent reverse transcription polymerase chain reaction (RT-PCR) validation of expression levels for selected genes. Microarray results were analysed by both functional and expression profile clustering. We identified a small number of genes at both the 30min and 1h timepoints that were either upregulated or downregulated with flow compared to no-flow control by twofold or more. From the group of genes upregulated at 30 min, we selected nine for RT-PCR confirmation. All were found to be upregulated by at least twofold. We identify a novel set of early response genes potentially involved in mediating the anabolic response of MC3T3 osteoblasts to flow, and provide functional groupings of these genes that may shed light on the relevant mechanosensory pathways involved.

Original languageEnglish (US)
Pages (from-to)605-616
Number of pages12
JournalPhilosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences
Volume368
Issue number1912
DOIs
Publication statusPublished - Feb 13 2010

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Keywords

  • CDNA microarrays
  • Cellular mechanotransduction
  • Fluid shear stress
  • Gene expression
  • Osteoblast

ASJC Scopus subject areas

  • Mathematics(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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