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.

Backgound: 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/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 aggrecanase 1 (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.