Mechanical stretch promotes mesenchymal stem cell-osteoblast lineage migration through activation of mammalian target of rapamycin/matrix metalloproteinases signaling pathway

doi:10.3969/j.issn.2095-4344.2015.32.003

Abstract

Abstract:

BACKGROUND: Distraction osteogenesis is one of the most important tissue engineering technologies. However, the exact signaling pathway controlling mesenchymal stem cell-osteoblast lineage (MSC-OB) migration during distraction osteogenesis has not yet been elucidated. More efforts should be paid to make a full understanding of the mechanism on MSC-OB lineage migration, which can improve the clinical efficacy of distraction osteogenesis.
OBJECTIVE: To evaluate the effects of mechanical stretch on the ability of MSC-OB mobility and expression of mammalian target of rapamycin (mTOR) signaling pathway as well as matrix metalloproteinases (MMPs) in MSC-OB, and to make clear the mechanism by which controls MSC-OB migration during distraction osteogenesis.
METHODS: Twelve Sprague-Dawley rats were randomized into two groups: experimental group (n=6), an in vivo
rat mandibular distraction osteogenesis model was established on the right side of rats; non-stretch group (n=6), only the mandibular resection was done but with no distraction osteogenesis. Immunohistochemical staining was used to detect phosphorylated mTOR expression in new osteotylus at 15 days after operation. In addition, an in vitro cell stretch model was made in the mandibular mesenchymal stem cells from healthy Sprague-Dawley rats under resting tension force (6%, 4 hours); no distraction was done in control group. The ability of MSC-OB mobility, the expression of mTOR, Raptor, p70S6K and MMPs were evaluated using experiment methods including immunohistochemistry staining, real-time PCR and scratch assay.
RESULTS AND CONCLUSION: The expression of phosphorylated mTOR in MSC-OB was upregulated in the mandibular bone callus of the stretch group than the non-stretch group (P < 0.05). In the in vitro experiments, MSC-OB applied with mechanical stretch (6%, 4 hours) showed elevated gene expression levels of mTOR, Raptor, p70S6K, MMP-2, MMP-9 and MMP-13 compared with the control group (0%, 4 hours). Meanwhile, MSC-OB in the experiment group (6%, 4 hours) showed a greater ability of mobility, as demonstrated by a farther distance after 48 hours of observation (P < 0.05). The present study suggests that the enhancement of MSC-OB mobility correlates with increase of the gene expression of MMPs and mTOR signaling pathway. Mechanical stretch may promote MSC-OB migration through activation of mTOR/MMPs signaling pathway.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Mandible, Mesenchymal Stem Cells, Osteogenesis, Stress, Mechanical

CLC Number:

R394.2

Yang Zi-hui, Wu Bao-lei, Jia Sen, Yang Xin-jie, Shan Chun, Liu Xiao-chang, Wang Lei, Lei De-lin . Mechanical stretch promotes mesenchymal stem cell-osteoblast lineage migration through activation of mammalian target of rapamycin/matrix metalloproteinases signaling pathway[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(32): 5097-5102.

Figures/Tables 2

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