Effect of Osteopontin on Nuclear Mechanics of Bone Marrow Mesenchymal Stem Cells and Its Involved Molecular Mechanisms
10.16156/j.1004-7220.2018.03.11
- VernacularTitle:骨桥蛋白对骨髓间充质干细胞核力学特性的影响及相关分子机制
- Author:
Zeyi QIAN
1
;
Zhiyue ZHENG
2
;
Guanbin SONG
2
Author Information
1. Chongqing Liangjiang Yucai Middle Schoo
2. College of Bioengineering, Chongqing University
- Publication Type:Journal Article
- Keywords:
osteopontin (OPN);
bone marrow mesenchymal stem cells (BMSCs);
nuclear mechanics;
FAK-ERK1/2 signaling pathway;
cell migration
- From:
Journal of Medical Biomechanics
2018;33(3):E255-E261
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effects of osteopontin (OPN) on the nuclear mechanics of bone marrow-derived mesenchymal stem cells (BMSCs) as well as its involved mechanisms. Methods The BMSC migration was evaluated using the Transwell assay. An atomic force microscope (AFM) was used to determine the elastic modulus of the BMSC nucleus and analyze the changes in the nuclear mechanics of the BMSCs after treatment with OPN. The activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase1/2 (ERK1/2) was measured by Western blot. The role of the FAK-ERK1/2 signaling pathway in mediating the OPN-affected BMSC nuclear mechanics was investigated by employing a specific inhibitor. RT-PCR and Western blot were used to detect the expression of Lamin A/C at mRNA and protein levels in the BMSCs, respectively. Results The elastic modulus of the BMSC nucleus exhibited a significant decrease after OPN treatment compared with that of the control group. OPN could upregulate the phosphorylation level of FAK and ERK1/2, but the inhibitor of FAK or ERK1/2 restored the OPN-decreased elastic modulus of the BMSC nucleus and inhibited the BMSC migration significantly. After treatment with OPN, the expression of Lamin A/C in the BMSCs reduced significantly, and such a reduced expression could be suppressed by the inhibitor of FAK or ERK1/2. Conclusions OPN could probably downregulate the expression of Lamin A/C of the BMSCs via the FAK-ERK1/2 signaling pathway, decrease the stiffness of the BMSC nucleus, and promote the migration of the BMSCs. The research outcomes provide the experimental evidence for further understanding the mechanism of the OPN-regulated BMSC migration and its potential clinical application.
