P2X7 receptor as sensitive flow sensor for ERK activation in osteoblasts.
Hisashi Okumura1, Dai Shiba, Toshikazu Kubo
1Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-0841, Japan.
Biochemical and Biophysical Research Communications
|May 27, 2008
Summary
Fluid flow stimulates ERK activation in osteoblasts, mediated by the P2X7 receptor (P2X7R). This pathway also increases c-fos mRNA, highlighting P2X7R
Area of Science:
- Biochemistry
- Cell Biology
- Mechanobiology
Background:
- Extracellular stimuli can activate intracellular signaling pathways in osteoblasts.
- Fluid flow is a significant mechanical stimulus for bone cells.
Purpose of the Study:
- To investigate the role of P2 receptors in ERK activation.
- To identify the specific P2 receptor subtype involved in fluid flow-induced signaling.
Main Methods:
- MC3T3-E1 osteoblasts were subjected to transient fluid flow.
- ERK activation was measured using Western blotting.
- P2 receptor antagonists and agonists were used to probe signaling pathways.
Main Results:
- Fluid flow induced ERK activation and increased c-fos mRNA expression.
- Non-selective P2 receptor antagonists and specific P2X7R antagonists inhibited ERK activation.
- P2X7R activation by BzATP mimicked fluid flow effects and was blocked by P2X7R antagonists.
- P2Y receptor inhibition did not affect fluid flow-induced ERK activation.
Conclusions:
- P2X7 receptor is a key mediator of ERK activation.
- Fluid flow signaling in osteoblasts is primarily mediated through the P2X7 receptor pathway.
