Cross-Coupling Effects of Silencing of Cyclooxygenase-2 (COX-2)/Aggrecanase-1 and Over-Expressed Insulin-Like Growth Factor 1 (IGF-1) in an Osteoarthritis Animal Model
Zhao Zhang, Xiaofei Li, Heng Huang, Guozhong Wang, Zhigang Qu, Haining Zhang
Department of Hand and Foot Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China (mainland)
Med Sci Monit 2017; 23:5302-5310
This study aimed to observe the effect of lentivirus-mediated cyclooxygenase-2 and aggrecanase-1 silencing and insulin-like growth factor-1 overexpression in human bone marrow mesenchymal stem cells after injection into model osteoarthritic knees.
MATERIAL AND METHODS: Using genetic recombination technique, the genes of cyclooxygenase-2, aggrecanase-1, and insulin-like growth factor-1 were recombined into the lentiviral vectors, and we transfected the human bone marrow stem cells in vitro. The BMSC transfected with lentivirus without genes served as a blank-virus group, and saline was used for another control group. One week later, the cytokines PGE2, aggrecanase-1, hIGF-1, and IL-1 were detected and compared between groups.
RESULTS: Compared with blank-virus group, the expression of COX-2 (85.81±5.12 ng/L) and aggrecanase1 (6.256±1.66) were decreased in the virus group (p<0.05), while the expression of hIGF-1 (17.46±1.86) was increased (p<0.05). The concentrations of PGE2 (85.81±5.12 ng/L), aggrecanase1 (51.34±5.463 ng/L), and IL-1 (82.31±4.321 ng/L) decreased (p<0.05) within the knee, but the concentration of hIGF-1 (44.33±0.7194 ng/L) increased (p<0.05). Compared with the other groups, the results of histological and immunohistochemical examinations demonstrated that the abrasion of articular cartilage was significantly improved and repaired.
CONCLUSIONS: Lentivirus-mediated RNAi can inhibit the expression of COX-2 mRNA and aggrecanase-1mRNA, and enhance the hIGF-1 mRNA expression, thereby influencing the concentration of cytokines in the early osteoarthritic model knee joints.
Keywords: Bone Marrow Cells, Cyclooxygenase 2, Insulin-Like Growth Factor Binding Protein 3