Purinergic signaling is required for fluid shear stress-induced NF-κB translocation in osteoblasts

Damian C Genetos, Norman J. Karin, Derik J. Geist, Henry J. Donahue, Randall L. Duncan

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-κB. We examined whether this process was under the control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-κB inhibitory protein IκBα and exhibited cytosolic localization of NF-κB. Under fluid shear stress, IκBα levels decreased, and concomitant nuclear localization of NF-κB was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in IκBα, and NF-κB remained within the cytosol. Similar results were found using oxidized ATP or Brilliant Blue G, P2X7 receptor antagonists, indicating that the P2X7 receptor is responsible for fluid shear-stress-induced IκBα degradation and nuclear accumulation of NF-κB. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced IκBα degradation. These phenomena involved neither ERK1/2 signaling nor autocrine activation by P2X7-generated lysophosphatidic acid. Our results suggest that fluid shear stress regulates NF-κB activity through the P2Y6 and P2X7 receptor.

Original languageEnglish (US)
Pages (from-to)737-744
Number of pages8
JournalExperimental Cell Research
Volume317
Issue number6
DOIs
StatePublished - Apr 1 2011

Fingerprint

Purinergic P2X7 Receptors
Osteoblasts
Autocrine Communication
Purinergic Receptors
Cytosol
Transcription Factors
Adenosine Triphosphate
Gene Expression
purinoceptor P2Y6

Keywords

  • ERK1/2
  • Lysophosphatidic acid
  • Mechanotransduction
  • NF-κB
  • Osteoblast
  • P2X7
  • P2Y6
  • Purinergic

ASJC Scopus subject areas

  • Cell Biology

Cite this

Purinergic signaling is required for fluid shear stress-induced NF-κB translocation in osteoblasts. / Genetos, Damian C; Karin, Norman J.; Geist, Derik J.; Donahue, Henry J.; Duncan, Randall L.

In: Experimental Cell Research, Vol. 317, No. 6, 01.04.2011, p. 737-744.

Research output: Contribution to journalArticle

Genetos, Damian C ; Karin, Norman J. ; Geist, Derik J. ; Donahue, Henry J. ; Duncan, Randall L. / Purinergic signaling is required for fluid shear stress-induced NF-κB translocation in osteoblasts. In: Experimental Cell Research. 2011 ; Vol. 317, No. 6. pp. 737-744.
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