Gao Heqi, Zhai Mingming, Wang Pan, Zhang Xuhui, Cai Jing, Chen Xiaofei, Shen Guanghao, Luo Erping, Jing Da
Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Mol Med Rep. 2017 Jul;16(1):317-324. doi: 10.3892/mmr.2017.6608. Epub 2017 May 19.
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 gn, 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 β‑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.
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疾病，其中成骨细胞和破骨细胞高度参与异常的骨重塑过程。最近，低强度、高频全身振动已在实验和临床中被证明能显著减轻骨质减少。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不清楚。本研究系统地研究了机械振动（0.5 gn，45 Hz）对体外原代成骨细胞的作用及其潜在的分子信号机制。本研究结果表明，低水平机械刺激促进了成骨细胞增殖和细胞外基质矿化。此外，还发现机械振动可改善原代成骨细胞的细胞骨架排列。此外，通过逆转录-定量聚合酶链反应（RT-qPCR）分析确定，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著增加，并抑制了硬化蛋白基因表达。观察到机械振动上调了包括骨钙素和Runt相关转录因子2在内的成骨相关生物标志物的基因和蛋白表达水平。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（包括Wnt3a、低密度脂蛋白受体相关蛋白6和β-连环蛋白）的基因和蛋白表达。总之，本研究表明机械振动刺激成骨细胞活性，可能通过潜在的经典Wnt信号相关机制发挥作用。这些发现提供了新的信息，有助于增进对机械振动响应中成骨细胞活性所涉及分子机制的理解，这可能有助于机械振动在临床上治疗骨质疏松症的科学应用。
