PMID- 32104269 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 1792-0981 (Print) IS - 1792-1015 (Electronic) IS - 1792-0981 (Linking) VI - 19 IP - 3 DP - 2020 Mar TI - Hyperhomocysteinemia inhibits tibial fracture healing in rats through PI3K/AKT signaling pathway. PG - 2083-2088 LID - 10.3892/etm.2020.8412 [doi] AB - To explore the influence of hyperhomocysteinemia (hHcys) on the tibial fracture healing in rats and its effect on the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT) signaling pathway. A total of 36 Sprague-Dawley rats were randomly divided into sham group (n=12), tibial fracture group (n=12) and hHcys + fracture group (n=12). The rats in tibial fracture group underwent the tibial fracture surgery, while the model of tibial fracture and hHcys was established in hHcys + fracture group. The level of plasma homocysteine (Hcy) in each group was analyzed using the full-automatic biochemical analyzer, the fracture stress biomechanical measurement was performed, and the ultimate bending strength and torque were calculated. Moreover, the protein expressions of PI3K and phosphorylated (p)-AKT in tibial tissues were detected using western blotting, the messenger ribonucleic acid (mRNA) levels of Bcl-2 associated X protein (Bax) and caspase-3 were detected using quantitative polymerase chain reaction (qPCR), the apoptosis was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and the expressions of inflammatory factors were detected via immunohistochemistry. Compared with sham group, tibial fracture group and hHcys + fracture group had a significantly increased level of plasma Hcy, significantly decreased ultimate bending strength and torque, obviously decreased relative protein expressions of PI3K and p-AKT, increased mRNA levels of Bax and caspase-3 and an increased expression of pro-inflammatory factor tumor necrosis factor-alpha (TNF-alpha). Compared with tibial fracture group, hHcys + fracture group had a higher level of plasma Hcy, lower ultimate bending strength and torque, lower relative protein expressions of PI3K and p-AKT, higher mRNA levels of Bax and caspase-3, a higher apoptosis rate and a higher expression of TNF-alpha. hHcys blocks the downstream apoptotic signal transduction, promotes apoptosis and inflammatory response, and affects fracture healing through affecting the PI3K/AKT signaling pathway. CI - Copyright: (c) Liu et al. FAU - Liu, Su AU - Liu S AD - Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China. FAU - Huang, Yunzong AU - Huang Y AD - Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China. FAU - Tian, Shoujing AU - Tian S AD - Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China. FAU - Zhang, Wei AU - Zhang W AD - Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China. FAU - Xu, Youjia AU - Xu Y AD - Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China. FAU - Ge, Jianfei AU - Ge J AD - Department of Orthopedics, The Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, Jiangsu 215600, P.R. China. LA - eng PT - Journal Article DEP - 20200103 PL - Greece TA - Exp Ther Med JT - Experimental and therapeutic medicine JID - 101531947 PMC - PMC7027308 OTO - NOTNLM OT - PI3K/AKT signaling pathway OT - hyperhomocysteinemia OT - inflammatory response OT - tibial fracture EDAT- 2020/02/28 06:00 MHDA- 2020/02/28 06:01 PMCR- 2020/01/03 CRDT- 2020/02/28 06:00 PHST- 2019/09/16 00:00 [received] PHST- 2019/11/11 00:00 [accepted] PHST- 2020/02/28 06:00 [entrez] PHST- 2020/02/28 06:00 [pubmed] PHST- 2020/02/28 06:01 [medline] PHST- 2020/01/03 00:00 [pmc-release] AID - ETM-0-0-8412 [pii] AID - 10.3892/etm.2020.8412 [doi] PST - ppublish SO - Exp Ther Med. 2020 Mar;19(3):2083-2088. doi: 10.3892/etm.2020.8412. Epub 2020 Jan 3.