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RhoA-Mediated Signaling in Mechanotransduction of Osteoblasts



Details

  • Personal Author:
  • Description:
    Osteoblasts play a pivotal role in load-driven bone formation by activating Wnt signaling through a signal from osteocytes as a mechanosensor. Osteoblasts are also sensitive to mechanical stimulation, but the role of RhoA, a small GTPase involved in the regulation of cytoskeleton adhesion complexes, in mechanotransduction of osteoblasts is not completely understood. Using MC3T3-E1 osteoblast-like cells under 1 hr flow treatment at 10 dyn/cm2, we examined a hypothesis that RhoA signaling mediates the cellular responses to flow-induced shear stress. To test the hypothesis, we conducted genome-wide pathway analysis and evaluated the role of RhoA in molecular signaling. Activity of RhoA was determined with a RhoA biosensor, which determined the activation state of RhoA based on a fluorescence resonance energy transfer between CFP and YFP fluorophores. A pathway analysis indicated that flow treatment activated phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling as well as a circadian regulatory pathway. Western blot analysis revealed that in response to flow treatment phosphorylation of Akt in PI3K signaling and phosphorylation of p38 and ERK1/2 in MAPK signaling were induced. FRET measurement showed that RhoA was activated by flow treatment, and an inhibitor to a Rho kinase significantly reduced flow-induced phosphorylation of p38, ERK1/2, and Akt as well as flow-driven elevation of the mRNA levels of osteopontin and cyclooxygenase-2. Collectively, the result demonstrates that in response to 1 hr flow treatment to MC3T3-E1 cells at 10 dyn/cm2, RhoA plays a critical role in activating PI3K and MAPK signaling as well as modulating the circadian regulatory pathway. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    0300-8207
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    398-406
  • Volume:
    53
  • Issue:
    5
  • NIOSHTIC Number:
    nn:20050217
  • Citation:
    Connect Tissue Res 2012 Sep/Oct; 53(5):398-406
  • Contact Point Address:
    Hiroki Yokota, PhD, Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, SL220C, 723 West Michigan Street, Indianapolis, IN 46202
  • Email:
    hyokota@iupui.edu
  • Federal Fiscal Year:
    2012
  • Performing Organization:
    University of Cincinnati
  • Peer Reviewed:
    True
  • Start Date:
    20050701
  • Source Full Name:
    Connective Tissue Research
  • End Date:
    20260630
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:07ad6505fba67e4a5bd405caced0b35a4f83431f1d9e61a80c77ee14c3664c5909cacc9d70a506e05794bfdb256d228956e66f6a5d0dd5eeeacd293f9470d654
  • Download URL:
  • File Type:
    Filetype[PDF - 978.41 KB ]
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