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07 November 2017 : Animal Research  

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 Zhang1ABCD, Xiaofei Li2ABCEF, Heng Huang1BD, Guozhong Wang1AB, Zhigang Qu1AD, Haining Zhang2ABCDG*

DOI: 10.12659/MSM.907150

Med Sci Monit 2017; 23:5302-5310

Abstract

BACKGROUND: 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

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750