AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells

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• 作者：Zhiguo Qu ; Shengnan Guo ; Guojun Fang ; Zhenghong Cui…
• 关键词：AKT ; hUC ; MSC ; BMP ; 2 ; OPG ; BSP ; BGP ; Nonunion
• 刊名：Cell Biochemistry and Biophysics
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：71
• 期：3
• 页码：1543-1551
• 全文大小：1,297 KB
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• 作者单位：Zhiguo Qu (1) (2)
  Shengnan Guo (2) (3)
  Guojun Fang (1) (2)
  Zhenghong Cui (1) (2)
  Ying Liu (3)
  
  1. Department of Orthopaedic Surgery, Siping Hospital Affiliated to China Medical University, Siping, Jilin, China
  2. Tuhua Bioengineering Company Ltd, Siping, Jilin, China
  3. Department of Stem Cell Clinical Application Centre, Siping Hospital Affiliated to China Medical University, No. 89, Nanyingbin Road, Tiexi District, Siping, 136000, Jilin, China
  
• 刊物主题：Biochemistry, general; Pharmacology/Toxicology; Biotechnology; Cell Biology; Biophysics and Biological Physics;
• 出版者：Springer US
• ISSN：1559-0283

文摘

We have previously grafted human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with blood plasma to treat rat tibia nonunion. To further examine the biological characteristics of this process, we applied an established hUC-MSCs-treated rat nonunion model with the addition of an inhibitor of AKT. SD rats (80) were randomly divided into four groups: a fracture group (positive control); a nonunion group (negative control); a hUC-MSCs grafting with blood plasma group; and a hUC-MSCs grafting with blood plasma & AKT blocker group. The animals were sacrificed under deep anesthesia at 4 and 8?weeks post fracture for analysis. The fracture line became less defined at 4?weeks and disappeared at 8?weeks postoperatively in both the hUC-MSCs grafting with blood plasma and grafting with blood plasma & the AKT blocker, which is similar to the fracture group. Histological immunofluorescence studies showed that the numbers of hUC-MSCs in the calluses were significantly higher in the hUC-MSCs grafting with blood plasma than those in group with the AKT blocker. More bone morphogenetic protein 2 and bone sialoprotein expression and less osteoprotegerin and bone gla protein expression were observed in the AKT blocker group compared to the hUC-MSCs grafting with blood plasma. AKT gene expression in the AKT blocker group was decreased 50?% compared to the hUC-MSCs with plasma group and decreased 70?% compared to the fracture group, while the elastic modulus was decreased. In summary, our work demonstrates that AKT may play a role in modulating osteogenesis induced by hUC-MSCs.