Low-level mechanical vibration enhances osteoblastogenesis via a canonical Wnt signaling-associated mechanism

摘要

Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low-magnitude, high-frequency whole-body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive. The current study systematically investigated the effect and potential molecular signaling mechanisms in mediating the effects of mechanical vibration (0.5 g(n), 45 Hz) on primary osteoblasts in vitro. The results of the present study demonstrated that low-level mechanical stimulation promoted osteoblastic proliferation and extracellular matrix mineralization. In addition, it was also revealed that mechanical vibration induced improved cytoskeleton arrangement in primary osteoblasts. Furthermore, mechanical vibration resulted in significantly increased gene expression of alkaline phosphatase, bone morphogenetic protein 2 and osteoprotegerin, and suppressed sclerostin gene expression, as determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Mechanical vibration was observed to upregulate gene and protein expression levels of osteogenesis-associated biomarkers, including osteocalcin and Runt-related transcription factor 2. In addition, RT-qPCR and western blotting analysis demonstrated that mechanical vibration promoted gene and protein expression of canonical Wnt signaling genes, including Wnt3a, low-density lipoprotein receptor-related protein 6 and beta-catenin. In conclusion, the present study demonstrated that mechanical vibration stimulates osteoblastic activities and may function through a potential canonical Wnt signaling-associated mechanism. These findings provided novel information that improves the understanding of the molecular mechanisms involved in osteoblastic activities in response to mechanical vibration, which may facilitate the scientific application of mechanical vibration for the treatment of osteoporosis in the clinic.