A Short Pulse of Mechanical Force Induces Gene Expression and Growth in MC3T3-E1 Osteoblasts via an ERK 1/2 Pathway

Abstract

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 -30g corresponds to physiological levels of 40 -300 strain. 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-␤, and 18s were unaffected by gravity loading. Short-term physiological loading induced extracellular signal-regulated kinase (ERK 1/2) phosphorylation in a dosedependent manner with maximum phosphorylation saturating at mechanical loading levels of 12g (p < 0.001) with no effect on total ERK. The phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical force.

Mechanical Strain on Osteoblasts Activates Autophosphorylation of Focal Adhesion Kinase and Proline-rich Tyrosine Kinase 2 Tyrosine Sites Involved in ERK Activation

“…Interestingly, Jessop et al found that ERK activation patterns differed between both stimuli (15). In addition, centrifugation, which has also been used as a mechanical stimulus in vitro, did induce ERK activation in MC3T3 cells; however, FAK phosphorylation did not occur in this model (13), whereas it was observed in our work. Altogether, these data demonstrate that, whereas various stimuli appear to be relevant in terms of bone physiology, they are not redundant in terms of molecular events Moreover, the type and stage of differentiation also modulate mechanically induced ERK acti- vation.…”

“…Recent reports demonstrated that mechanical strain is able to activate ERK1/2 in several adherent cells such as mesangial cells (6), smooth muscle cells (7), and chondrocytes (8). In osteoblasts, ERK activation was mostly reported in fluid flow (9 -12), centrifugation (13), or magnetic drag force (14) experiments and in only one study using cyclic stretch (albeit combined with fluid flow) (15). However, cell stretch appears to be a relevant model of mechanical stimulus in the bone field (16,17) and provides specific osteoblastic responses (18).…”

Optimal Intensity Shock Wave Promotes the Adhesion and Migration of Rat Osteoblasts via Integrin β1-mediated Expression of Phosphorylated Focal Adhesion Kinase

“…Many studies have shown that effective physical stimulation could induce a series of biological changes in osteoblasts, such as osteogenic effect (58,59), alteration of gene expression (44,60), and related signal pathway changes (44,61). The beneficial effects for enhanced osteoblast adhesion and migration may result from reorganization of actin cytoskeleton to a certain degree (23).…”

Mechanomics and Physicomics in Gravisensing

“…Although physical processes, and therefore biological systems, are behaving differently under (near) weightlessness (Albrecht-Buehler 1991;Todd 1989;van Loon 2007c) including studies under hypergravity c.q. hyper-weight conditions provide information for the entire gravity spectrum (Hatton et al 2003;Hemmersbach and Haeder 1999;Thoumine et al 1996;Searby et al 2005;Tabony 2004;van Loon et al 1999). It was at first argued from a purely physical point of view, that non-specialized single cells might not be susceptible to small forces such as gravity (Pollard 1965;Went 1968), many studies have shown otherwise.…”