Cyclic fluid shear stress promotes osteoblastic cells proliferation through ERK5 signaling pathway

Mol Cell Biochem. 2012 May;364(1-2):321-7. doi: 10.1007/s11010-012-1233-y.


Fluid shear stress plays an important role in bone remodeling, however, the mechanism of mechanotransduction in bone tissue remains unclear. Recently, ERK5 has been found to be involved in multiple cellular processes. This study was designed to investigate the potential involvement of ERK5 in the proliferative response of osteoblastic cells to cyclic fluid shear stress. We reported here that cyclic fluid shear stress promoted ERK5 phosphorylation in MC3T3-E1 cells. Inhibition of ERK5 phosphorylation attenuated the increased expression of AP-1 and cyclin D1 and cell proliferation induced by cyclic fluid flow, but promoted p-16 expression. Further more, we found that cyclic fluid shear stress was a better stimuli for ERK5 activation and cyclin D1 expression compared with continuous fluid shear stress. Moreover, the pharmacological ERK5 inhibitor, BIX02189, which inhibited ERK5 phosphorylation in a time-dependent manner and the suppression lasted for at least 4 h. Taken together, we demonstrate that ERK5/AP-1/cyclin D1 pathway is involved in the mechanism of osteoblasts proliferation induced by cyclic fluid shear stress, which is superior in promoting cellular proliferation compared with continuous fluid shear stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / pharmacology
  • Animals
  • Cell Line
  • Cell Proliferation*
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism*
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics*
  • Hydrogen Peroxide / pharmacology
  • Indoles / pharmacology
  • Mice
  • Mitogen-Activated Protein Kinase 7 / genetics
  • Mitogen-Activated Protein Kinase 7 / metabolism*
  • Osteoblasts / enzymology
  • Osteoblasts / metabolism*
  • Phosphorylation / drug effects
  • Signal Transduction
  • Stress, Mechanical
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism


  • Aniline Compounds
  • BIX 02189
  • Cyclin-Dependent Kinase Inhibitor p16
  • Indoles
  • Transcription Factor AP-1
  • Cyclin D1
  • Hydrogen Peroxide
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 4
  • Mitogen-Activated Protein Kinase 7