title: Whole body vibration improves osseointegration by up-regulating osteoblastic activity but down-regulating osteoblast-mediated osteoclastogenesis via ERK1/2 pathway.
abstract: Due to the reduction in bone mass and deterioration in bone microarchitecture, osteoporosis is an important risk factor for impairing implant osseointegration. Recently, low-magnitude, high-frequency (LMHF) vibration (LM: <1×g; HF: 20-90Hz) has been shown to exhibit anabolic, but anti-resorptive effects on skeletal homeostasis. Therefore, we hypothesized that LMHF loading, in terms of whole body vibration (WBV), may improve implant fixation under osteoporotic status. In the in vivo study, WBV treatment (magnitude: 0.3g, frequency: 40Hz, time: 30min/12h, 5days/week) was applied after hydroxyapatite-coated titanium implants were inserted in the bilateral tibiae of ovariectomized rats. The bone mass and the osteospecific gene expressions were measured at 12weeks post implantation. In the in vitro study, the cellular and molecular mechanisms underlying osteoblastic and osteoclastic activities were fully investigated using various experimental assays. Micro-CT examination showed that WBV could enhance osseointegration by improving microstructure parameters surrounding implants. WBV-regulated gene levels in favor of bone formation over resorption may be the reason for the favorable adaptive bone remolding on bone-implant surface. The in vitro study showed that vibration (magnitude: 0.3g, frequency: 40Hz, time: 30min/12h) up-regulated osteoblast differentiation, matrix synthesis and mineralization. However, mechanically regulated osteoclastic activity was mainly through the effect on osteoblastic cells producing osteoclastogenesis-associated key soluble factors, including RANKL and M-CSF. Osteoblasts were therefore the direct target cells during the mechanotransduction process. The ERK1/2 pathway was demonstrated to play an essential role in vibration-induced enhancement of bone formation and decreased bone resorption. Our data suggests that WBV was a helpful non-pharmacological intervention for improving osseointegration under osteoporosis.
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Yan'an Road 395, Hangzhou 310000, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Yan'an Road 395, Hangzhou 310000, People's Republic of China.
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Guan
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Yan'an Road 395, Hangzhou 310000, People's Republic of China.
authors.forename: Tie
authors.initials: T
authors.lastname: Liu
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Yan'an Road 395, Hangzhou 310000, People's Republic of China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Yan'an Road 395, Hangzhou 310000, People's Republic of China.
authors.forename: Mengfei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Yan'an Road 395, Hangzhou 310000, People's Republic of China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Yang
authors.affiliation: Affiliated Hospital of Stomatology, Medical College, Zhejiang University, Yan'an Road 395, Hangzhou 310000, People's Republic of China. Electronic address: huimingwang1960@163.com.
authors.forename: Huiming
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D020935:MAP Kinase Signaling System; D016348:Osseointegration; D010006:Osteoblasts / Q000378:metabolism*; D010010:Osteoclasts / Q000201:enzymology*; D010012:Osteogenesis; D010052:Ovariectomy; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013977:Tibia / Q000000981:diagnostic imaging; D015854:Up-Regulation; D014732:Vibration; D055114:X-Ray Microtomography
keywords: Implant; Osseointegration; Osteoblast; Osteoclast precursors; Osteoporosis; Whole body vibration