PMID- 25413962 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20181202 IS - 1559-0283 (Electronic) IS - 1085-9195 (Print) IS - 1085-9195 (Linking) VI - 71 IP - 3 DP - 2015 Apr TI - AKT Pathway Affects Bone Regeneration in Nonunion Treated with Umbilical Cord-Derived Mesenchymal Stem Cells. PG - 1543-51 LID - 10.1007/s12013-014-0378-6 [doi] AB - 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. FAU - Qu, Zhiguo AU - Qu Z AD - Department of Orthopaedic Surgery, Siping Hospital Affiliated to China Medical University, Siping, Jilin, China. AD - Tuhua Bioengineering Company Ltd, Siping, Jilin, China. FAU - Guo, Shengnan AU - Guo S AD - Tuhua Bioengineering Company Ltd, Siping, Jilin, China. AD - Department of Stem Cell Clinical Application Centre, Siping Hospital Affiliated to China Medical University, No. 89, Nanyingbin Road, Tiexi District, Siping, 136000, Jilin, China. FAU - Fang, Guojun AU - Fang G AD - Department of Orthopaedic Surgery, Siping Hospital Affiliated to China Medical University, Siping, Jilin, China. AD - Tuhua Bioengineering Company Ltd, Siping, Jilin, China. FAU - Cui, Zhenghong AU - Cui Z AD - Department of Orthopaedic Surgery, Siping Hospital Affiliated to China Medical University, Siping, Jilin, China. AD - Tuhua Bioengineering Company Ltd, Siping, Jilin, China. FAU - Liu, Ying AU - Liu Y AD - 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. LA - eng PT - Journal Article PL - United States TA - Cell Biochem Biophys JT - Cell biochemistry and biophysics JID - 9701934 RN - 0 (Enzyme Inhibitors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Biomechanical Phenomena/drug effects MH - *Bone Regeneration/drug effects MH - Cell Adhesion MH - Cell Differentiation MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation, Enzymologic/drug effects MH - Humans MH - *Mesenchymal Stem Cell Transplantation MH - *Mesenchymal Stem Cells/cytology MH - Osteogenesis/drug effects MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/drug effects MH - Tibial Fractures/pathology/physiopathology/surgery MH - Umbilical Cord/*cytology PMC - PMC4449366 OTO - NOTNLM OT - AKT OT - BGP OT - BMP-2 OT - BSP OT - Nonunion OT - OPG OT - hUC-MSC EDAT- 2014/11/22 06:00 MHDA- 2016/12/15 06:00 PMCR- 2014/11/21 CRDT- 2014/11/22 06:00 PHST- 2014/11/22 06:00 [entrez] PHST- 2014/11/22 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2014/11/21 00:00 [pmc-release] AID - 10.1007/s12013-014-0378-6 [pii] AID - 378 [pii] AID - 10.1007/s12013-014-0378-6 [doi] PST - ppublish SO - Cell Biochem Biophys. 2015 Apr;71(3):1543-51. doi: 10.1007/s12013-014-0378-6.