title: AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Siping Hospital Affiliated to China Medical University, Siping, Jilin, China.|Tuhua Bioengineering Company Ltd, Siping, Jilin, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Qu
authors.affiliation: Tuhua Bioengineering Company Ltd, Siping, Jilin, China.|Department of Stem Cell Clinical Application Centre, Siping Hospital Affiliated to China Medical University, No. 89, Nanyingbin Road, Tiexi District, Siping, 136000, Jilin, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Orthopaedic Surgery, Siping Hospital Affiliated to China Medical University, Siping, Jilin, China.|Tuhua Bioengineering Company Ltd, Siping, Jilin, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Fang
authors.affiliation: Department of Orthopaedic Surgery, Siping Hospital Affiliated to China Medical University, Siping, Jilin, China.|Tuhua Bioengineering Company Ltd, Siping, Jilin, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Cui
authors.affiliation: Department of Stem Cell Clinical Application Centre, Siping Hospital Affiliated to China Medical University, No. 89, Nanyingbin Road, Tiexi District, Siping, 136000, Jilin, China. ly3641829@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001861:Bone Regeneration / Q000187:drug effects; D002448:Cell Adhesion; D002454:Cell Differentiation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013978:Tibial Fractures / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D004791:Enzyme Inhibitors; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; BGP; BMP-2; BSP; Nonunion; OPG; hUC-MSC