Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in A PKCζ-dependent manner

Jason W. Triplett, Rita O'Riley, Kristyn Tekulve, Suzanne M. Norvell, Fredrick Pavalko

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Maintenance of optimal bone physiology requires the coordinated activity of osteoclasts that resorb old bone and osteoblasts that deposit new bone. Mechanical loading of bone and the resulting movement of interstitial fluid within the spaces surrounding bone cells is thought to play a key role is maintaining optimal bone mass. One way in which fluid movement may promote bone formation is by enhancing osteoblast survival. We have shown previously that application of fluid flow to osteoblasts in vitro confers a protective effect by inhibiting osteoblast apoptosis (Pavalko et al., 2003, J. Cell Physiol., 194: 194-205). To investigate the cellular mechanisms that regulate the response of osteoblasts to fluid shear stress, we have examined the possible interaction between fluid flow and growth factors in MC3T3-E1 osteoblast-like cells. We found that insulin-like growth factor-I (IGF-I) was significantly more effective at preventing TNF-α-induced apoptosis when cells were first subjected to mechanical loading by exposure to either unidirectional or oscillatory fluid flow compared to cells that were maintained in static culture. Additionally, downstream signaling in response to treatment with IGF-I, including ERK and Akt activation, was enhanced in cells that were subjected to fluid flow, compared to cells maintained in static culture. Furthermore, we found that PKCζ activity is essential for fluid shear stress sensitization of IGF-IR, since a specific inhibitor of PCKζ function blocked the flow-enhanced IGF-I-activated Akt and ERK phosphorylation. Together, our results suggest that fluid shear stress may regulate IGF-I signaling in osteoblasts in a PKCζ-dependent manner.

Original languageEnglish
Pages (from-to)13-25
Number of pages13
JournalMCB Molecular and Cellular Biomechanics
Volume4
Issue number1
StatePublished - Mar 2007

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IGF Type 1 Receptor
Osteoblasts
Insulin-Like Growth Factor I
Bone and Bones
Apoptosis
Extracellular Fluid
Osteoclasts
Osteogenesis
Intercellular Signaling Peptides and Proteins
Maintenance
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology
  • Biophysics
  • Molecular Biology
  • Molecular Medicine

Cite this

Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in A PKCζ-dependent manner. / Triplett, Jason W.; O'Riley, Rita; Tekulve, Kristyn; Norvell, Suzanne M.; Pavalko, Fredrick.

In: MCB Molecular and Cellular Biomechanics, Vol. 4, No. 1, 03.2007, p. 13-25.

Research output: Contribution to journalArticle

Triplett, Jason W. ; O'Riley, Rita ; Tekulve, Kristyn ; Norvell, Suzanne M. ; Pavalko, Fredrick. / Mechanical loading by fluid shear stress enhances IGF-1 receptor signaling in osteoblasts in A PKCζ-dependent manner. In: MCB Molecular and Cellular Biomechanics. 2007 ; Vol. 4, No. 1. pp. 13-25.
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