In addition to systemic and local factors, mechanical strain plays a crucial role in bone remodeling during growth, development, and fracture healing, and especially in orthodontic tooth movement. Although many papers have been published oil the effects of mechanical stress oil osteoblasts or osteoblastic cells, little is known about the effects of different magnitudes of mechanical strain oil such cells. In the present Study, we investigated how different magnitudes of cyclic tensile strain affected osteoblasts. MCT3-E1 osteoblastic cells were subjected to 0%, 6%, 12% or 18% elongation for 24 h using a Flexercell Strain Unit, and then the mRNA and protein expressions of osteoprotegerin (OPG) and receptor activator of nuclear Factor-kappa B ligand (RANKL) were examined. The results showed that cyclic tensile strain induced a magnitude-dependent increase (0% 6%, 12%, and 18%) in OPG synthesis and a concomitant decrease in RANKL mRNA expression and sRANKL release from the osteoblasts. Furthermore, the induction of OPG mRNA expression by stretching was inhibited by indomethacin or genistein.. and the stretch-induced reduction of RANKL mRNA was inhibited by PD098059. These results indicate that different magnitudes of cyclic tensile strain influence the biological behavior of osteoblasts, which profoundly affects bone remodeling. (c) 2006 Elsevier Inc. All rights reserved.