Low-level mechanical vibration enhances osteoblastogenesis via a canonical Wnt signaling-associated mechanism
Low-level mechanical vibration enhances osteoblastogenesis via a canonical Wnt signaling-associated mechanism
复制标题
低水平机械振动通过典型的 Wnt 信号传导相关机制增强成骨细胞生成。
DOI：
10.3892/mmr.2017.6608
复制
发表时间：
2017-07-01
影响因子：
3.4
通讯作者：
Jing, Da
中科院分区：
文献类型：
--
作者：
Gao, Heqi;Zhai, Mingming;Jing, Da
骨质疏松症是一种以骨量减少和骨折易感性高为特征的骨骼代谢性疾病，其中成骨细胞和破骨细胞高度参与异常的骨重建过程。最近，低幅度，高频率的全身振动已被证明可以显着减少骨质疏松症的实验和临床。然而，当骨组织适应机械振动时，成骨细胞活性如何改变的潜在机制仍然难以捉摸。本研究系统地研究了机械振动（0.5g（n），45 Hz）对体外培养的原代成骨细胞的影响及其可能的分子信号转导机制。本研究的结果表明，低水平的机械刺激促进成骨细胞增殖和细胞外基质矿化。此外，还揭示了机械振动诱导原代成骨细胞中细胞骨架排列的改善。此外，机械振动导致碱性磷酸酶，骨形态发生蛋白2和骨保护素的基因表达显着增加，并抑制sclerostin基因表达，通过逆转录-定量聚合酶链反应（RT-qPCR）分析确定。观察到机械振动上调成骨相关生物标志物的基因和蛋白质表达水平，包括骨钙素和Runt相关转录因子2。此外，RT-qPCR和蛋白质印迹分析表明，机械振动促进了经典Wnt信号基因的基因和蛋白质表达，包括Wnt 3a、低密度脂蛋白受体相关蛋白6和β-连环蛋白。总之，本研究表明，机械振动刺激成骨细胞的活动，并可能通过一个潜在的经典Wnt信号相关机制发挥作用。这些发现为深入了解机械振动作用下成骨细胞活性的分子机制提供了新的信息，为机械振动治疗骨质疏松症的临床应用提供了科学依据。
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.