Purinergic Signaling is Required for Fluid Shear Stress-Induced NF-kB Translocation in Osteoblasts
Fluid shear stress regulates gene expression in osteoblasts, in part by activation of the transcription factor NF-kB. We examined whether this process was under control of purinoceptor activation. MC3T3-E1 osteoblasts under static conditions expressed the NF-kB inhibitory protein IkB alpha and exhibited cytosolic localization of NF-kB. Under fluid shear stress, IκBα levels decreased, and concomitant nuclear localization of NF-kB was observed. Cells exposed to fluid shear stress in ATP-depleted medium exhibited no significant reduction in IκBα, and NF-kB 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-kB. Pharmacologic blockage of the P2Y6 receptor also prevented shear-induced IkB alpha 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-kB activity through the P2Y6 and P2X7 receptor.
- Research Organization:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- AC05-76RL01830
- OSTI ID:
- 1011785
- Report Number(s):
- PNNL-SA-72626; 400412000; TRN: US201109%%601
- Journal Information:
- Experimental Cell Research, 317(6):737-744, Vol. 317, Issue 6; ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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