Compressive Force Induces the Expression of Bone Remodeling-Related Proteins via Interleukin-11 Production in MC3T3-E1 Cells

Abstract

In bone remodeling during orthodontic tooth movement, osteoblasts are closely related to bone matrix formation and osteoclast differentiation. Interleukin (IL)-11 is known to be a regulating factor of bone remodeling. Our previous study showed that compressive force (CF) induced IL-11 production in osteoblastic Saos-2 cells. Therefore, we examined the effect of CF on the expression of IL-11 receptor (IL-11r), IL-11, Runx2, bone morphogenetic protein (BMP)-2, receptor activator of NF-κB ligand (RANKL), macrophage colony-stimulating factor (M-CSF), and osteoprotegerin (OPG) using MC3T3-E1 cells as osteoblasts. To confirm the participation of autocrine mechanisms by CF-induced IL-11, we also examined the effect of CF on expression in the presence and absence of IL-11 antagonist. MC3T3-E1 cells were cultured with or without continuous CF (1.0 or 2.0 g/ cm2) in the presence or absence of IL-11 antagonist for up to 24 h. The expression of the IL-11r, IL-11, Runx2, BMP-2, RANKL, M-CSF, and OPG genes was estimated by determining mRNA levels by real-time PCR; protein expression was examined by ELISA or Western blotting. CF increased the expression of IL-11r and IL-11; the maximum level of these expressions was achieved with CF at 2.0 g/cm2. CF also increased the expression of Runx2 and BMP-2; the maximum level of these expressions was achieved in CF at 1.0 g/cm2. IL-11 antagonist blocked the stimulatory effects of CF at 1.0 or 2.0 g/cm2 on the expression of Runx2, BMP-2, RANKL, and M-CSF but not on the expression of IL-11r, IL-11, and OPG. These results suggest that CF at 1.0 g/cm2 increases the expression of proteins related to bone formation, such as Runx2 and BMP-2, via the autocrine mechanism of CF-induced IL-11 in osteoblasts, whereas CF at 2.0 g/cm2 increases the expression of RANKL and M-CSF that promotes osteoclast formation via CF-induced IL-11. These results also suggest that the balance of bone remodeling changes according to the strength of CF.