Premium
A Short Pulse of Mechanical Force Induces Gene Expression and Growth in MC3T3‐E1 Osteoblasts via an ERK 1/2 Pathway
Author(s) -
Hatton Jason P,
Pooran Milad,
Li ChaiFei,
Luzzio Chris,
HughesFulford Millie
Publication year - 2003
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2003.18.1.58
Subject(s) - mapk/erk pathway , kinase , phosphorylation , p38 mitogen activated protein kinases , extracellular , focal adhesion , microbiology and biotechnology , gene expression , chemistry , endocrinology , medicine , biology , gene , biochemistry
Physiological mechanical loading is crucial for maintenance of bone integrity and architecture. We have calculated the strain caused by gravity stress on osteoblasts and found that 4–30 g corresponds to physiological levels of 40–300 μstrain. Short‐term gravity loading (15 minutes) induced a 15‐fold increase in expression of growth‐related immediate early gene c‐ fos , a 5‐fold increase in egr‐1 , and a 3‐fold increase in autocrine bFGF . The non‐growth‐related genes EP‐1 , TGF‐β , and 18s were unaffected by gravity loading. Short‐term physiological loading induced extracellular signal‐regulated kinase (ERK 1/2) phosphorylation in a dose‐dependent manner with maximum phosphorylation saturating at mechanical loading levels of 12 g ( p < 0.001) with no effect on total ERK. The phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical force. g ‐Loading did not activate P38 MAPK or c‐jun N‐terminal kinase (JNK). Additionally, a gravity pulse resulted in the localization of phosphorylated ERK 1/2 to the nucleus; this did not occur in unloaded cells. The induction of c‐ fos was inhibited 74% by the MEK1/2 inhibitor U0126 ( p < 0.001) but was not affected by MEK1 or p38 MAPK‐specific inhibitors. The long‐term consequence of a single 15‐minute gravity pulse was a 64% increase in cell growth ( p < 0.001). U0126 significantly inhibited gravity‐induced growth by 50% ( p < 0.001). These studies suggest that short periods of physiological mechanical stress induce immediate early gene expression and growth in MC3T3‐E1 osteoblasts primarily through an ERK 1/2‐mediated pathway.