It has been proven that mechanical stretch plays an important role in regulating proliferation of mesenchymal stem cells (MSCs). However, the mechanisms that link mechanical stretch and MSCs proliferation are poorly understood. In this study, using a custom-made cell-stretching device, we explored the signal molecule which might be involved in the mechanical stretch-induced proliferation of rat MSCs (rMSCs). We found that rMSCs, when subjected to 1 Hz, 10% strain for 15 min, exhibited a significant increase of cell proliferation. The stretched cells also expressed obvious increased mRNA for c-
. No significant difference was found in total expression of extracellular signal-regulated kinase 1/2 (t-ERK1/2) at protein level, however, the phosphorylation of ERK1/2 (p-ERK1/2) was markedly increased after stretch. Pretreatment of rMSCs with PD98059, a specific inhibitor of the ERK1/2 activity, led to suppression of stretch-induced p-ERK1/2 and mRNA expression of c-
. Moreover, PD98059 abolished the stretch-induced proliferation of rMSCs. Taken together, these findings suggest that mechanical stretch is an effective approach to promoting proliferation of rMSCs in vitro, and ERK1/2 is a key mediator for stretch-induced proliferation in rMSCs.