MAP kinase and calcium signaling mediate fluid flow-induced human mesenchymal stem cell proliferation

Ryan C. Riddle, Amanda F. Taylor, Damian C. Genetos, Henry J. Donahue

Research output: Contribution to journalArticlepeer-review

158 Scopus citations


Mechanical signals are important regulators of skeletal homeostasis, and strain-induced oscillatory fluid flow is a potent mechanical stimulus. Although the mechanisms by which osteoblasts and osteocytes respond to fluid flow are being elucidated, little is known about the mechanisms by which bone marrow-derived mesenchymal stem cells respond to such stimuli. Here we show that the intracellular signaling cascades activated in human mesenchymal stem cells by fluid flow are similar to those activated in osteoblastic cells. Oscillatory fluid flow inducing shear stresses of 5, 10, and 20 dyn/cm2 triggered rapid, flow rate-dependent increases in intracellular calcium that pharmacological studies suggest are inositol trisphosphate mediated. The application of fluid flow also induced the phosphorylation of extracellular signal-regulated kinase-1 and -2 as well as the activation of the calcium-sensitive protein phosphatase calcineurin in mesenchymal stem cells. Activation of these signaling pathways combined to induce a robust increase in cellular proliferation. These data suggest that mechanically induced fluid flow regulates not only osteoblastic behavior but also that of mesenchymal precursors, implying that the observed osteogenic response to mechanical loading may be mediated by alterations in the cellular behavior of multiple members of the osteoblast lineage, perhaps by a common signaling pathway.

Original languageEnglish (US)
Pages (from-to)C776-C784
JournalAmerican Journal of Physiology - Cell Physiology
Issue number3
StatePublished - Mar 2006
Externally publishedYes


  • Bone
  • Marrow
  • Mechanotransduction

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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