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Different effects of intermittent and continuous fluid shear stresses on osteogenic differentiation of human mesenchymal stem cells
Authors:Liyue Liu  Bin Yu  Jiarong Chen  Zihua Tang  Chen Zong  Dan Shen  Qiang Zheng  Xiangming Tong  Changyou Gao  Jinfu Wang
Institution:1. Institute of Cell Biology, College of Life Sciences, Zhejiang University, Hangzhou, 310058, People’s Republic of China
3. Laboratory of Bone Marrow, The First Hospital, Zhejiang University, Hangzhou, Zhejiang, 310006, People’s Republic of China
4. Institute of Orthopedics, The Second Hospital, Zhejiang University, Hangzhou, Zhejiang, 310009, People’s Republic of China
2. Institute of Medical Materials, College of Material and Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310028, People’s Republic of China
Abstract:A reasonable mechanical microenvironment similar to the bone microenvironment in vivo is critical to the formation of engineering bone tissues. As fluid shear stress (FSS) produced by perfusion culture system can lead to the osteogenic differentiation of human mesenchymal stem cells (hMSCs), it is widely used in studies of bone tissue engineering. However, effects of FSS on the differentiation of hMSCs largely depend on the FSS application manner. It is interesting how different FSS application manners influence the differentiation of hMSCs. In this study, we examined the effects of intermittent FSS and continuous FSS on the osteogenic differentiation of hMSCs. The phosphorylation level of ERK1/2 and FAK is measured to investigate the effects of different FSS application manners on the activation of signaling molecules. The results showed that intermittent FSS could promote the osteogenic differentiation of hMSCs. The expression level of osteogenic genes and the alkaline phosphatase (ALP) activity in cells under intermittent FSS application were significantly higher than those in cells under continuous FSS application. Moreover, intermittent FSS up-regulated the activity of ERK1/2 and FAK. Our study demonstrated that intermittent FSS is more effective to induce the osteogenic differentiation of hMSCs than continuous FSS.
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