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| Effects of stromal cell-derived factor-1α overexpression on migration of mesenchymal stem cells under extreme hypoxia |
| WANG Hui1 XU Liangliang2 SUN Daming2 MENG Yi2 ZHANG Chenglong1 XU Haijia1 NING Yu3 LI Zhanghua1 |
1.Department of Orthopaedics, Tongren Hospital of Wuhan University, Hubei Province, Wuhan 430000, China;
2.Graduate School, Wuhan Sports University, Hubei Province, Wuhan 430000, China;
3.Department of Orthopaedics, Xiangyang Hospital of Traditional Chinese Medicine, Hubei Province, Xiangyang 441000, China |
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Abstract Objective To investigate the effects of stromal cell-derived factor-1α (SDF-1α) overexpression on migration of mesenchymal stem cells (MSCs) under extreme hypoxia. Methods MSCs derived from two normal male Japanese white rabbits (two weeks of age, body weight [250±30] g) were divided into blank group (no intervention), AMD3100 group (added CXC subfamily receptor 4 [CXCR4] specific inhibitor AMD3100), SDF-1α adenovirus (Ad-SDF-1α) group (Ad-SDF-1α transfected), and Ad-SDF-1α+AMD3100 group (Ad-SDF-1α transfected and added AMD3100). The four groups were cultured under extreme hypoxia (1%) for 48 h, and the changes of migration ability were detected by Transwell experiment. The mRNA and protein expressions of HIF-1α, vascular endothelial growth factor (VEGF), and CXCR4 were detected by real-time quantitative PCR and Western blot. Results MSCs adhered to the wall in spindle and polygonal shape, and showed clonal growth. Uniform and bright green fluorescence could be observed after transfection with Ad-SDF-1α. The optical density (OD) value of AMD3100 group was lower than that of blank group, OD value of Ad-SDF-1α group was higher than that of blank group, OD value of Ad-SDF-1α+AMD3100 group was higher than that of AMD3100 group and lower than that of Ad-SDF-1α group, the differences were statistically significant (P ＜ 0.05). The mRNA expressions of VEGF and CXCR4 in AMD3100 group were lower than those in blank group, while the mRNA expressions of HIF-1α, VEGF, and CXCR4 in Ad-SDF-1α group were higher than those in blank group, the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01). The mRNA expressions of VEGF and CXCR4 in Ad-SDF-1α+AMD3100 group were higher than those in AMD3100 group, while the mRNA expressions of HIF-1α, VEGF, and CXCR4 were lower than those in Ad-SDF-1α group, the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01). The protein expressions of HIF-1α, VEGF, and CXCR4 in AMD3100 group were lower than those in blank group, while the protein expressions of HIF-1α, VEGF, and CXCR4 in Ad-SDF-1α group were higher than those in blank group, the protein expressions of HIF-1α, VEGF, and CXCR4 in Ad-SDF-1α+AMD3100 group were higher than those in AMD3100 group and lower than those in Ad-SDF-1α group, the differences were statistically significant (P ＜ 0.05 or P ＜ 0.01). Conclusion SDF-1α overexpression can still promote MSCs migration under extreme hypoxia, and reverse the inhibitory effect of AMD3100 to some extent.
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