Effects of low-magnitude high-frequency vibration on osteoblasts are dependent on estrogen receptor alpha signaling and cytoskeletal remodeling

摘要

Clinical and experimental studies demonstrate the potential of low-magnitude high-frequency vibration (LMHFV) to enhance bone formation in the intact skeleton and during fracture healing. Moreover, it was shown that the effects of vibration therapy during fracture healing are highly dependent on the estrogen status of the vibrated individual and that estrogen receptor (ER) alpha signaling plays a major role in mechanotransduction of LMHFV. Because it is known that LMHFV can directly act on osteogenic cells, we hypothesize that the differential effects of LMHFV in the presence and absence of estrogen are mediated by ER alpha signaling in osteoblasts. To prove this hypothesis, we subjected preosteoblastic MC3T3-E1 cells and primary osteoblasts to LMHFV in vitro. We found increased Cox2 gene expression, cell metabolic activity and cell proliferation after LMHFV in the absence of estrogen, whereas the effects were contrary in the presence of estrogen. Blocking of ER alpha signaling by Esr1-siRNA knockdown or adding the selective ER alpha antagonist MPP dihydrochloride abolished the effects of LMHFV on osteoblast proliferation and Cox2 expression. Furthermore, primary osteoblasts isolated from ER alpha-knockout mice did not show a response towards LMHFV in the presence of estrogen. Additionally, blocking of actin cytoskeletal remodeling by adding the p160ROCK inhibitor Y-27632 abolished the effects of LMHFV. In contrast, expression of primary cilium was not necessary for mechanotransduction of LMHFV. These results suggest that direct effects of LMHFV on osteoblasts are dependent on ER alpha signaling and cytoskeletal remodeling. (C) 2018 Elsevier Inc. All rights reserved.