Abstract
BACKGROUND: To investigate the therapeutic effect of intraarticular injection of mesenchymal stem cells (MSC) in a rabbit osteoarthritis (OA) model. And to suppose whether MSC play a pivotal role in OA therapy by improving oxidative stress through secreting superoxide dismutase (SOD). METHODS: MSC and chondrocytes were isolated and cultured in vitro. SOD gene of MSC was silenced by siRNA technology to prepare the SOD-siRNA-MSC for in-vivo study. Twenty healthy adult New Zealand white rabbits underwent papain injection to induce OA and then received intra-articular injection with MSC, siRNA-MSC, or normal saline. The rabbits were divided into 4 groups (n = 5), such as the control group, the model group, the MSC group, the siRNA-MSC group. Cytokines determination was performed 2 and 4 weeks after treatment. Magnetic resonance imaging (MRI) and histopathology and immunohistochemistry determination were performed 4 weeks after treatment. Normal chondrocytes, OA chondrocytes, OA chondrocytes + MSC group, and OA chondrocytes + siRNA-MSC were incubated for 24 h. Then β-galactosidase staining and reactive oxygen species (ROS) level was detected to establish the senescence of the cells. RESULTS: COMP, TNF-α, MMP-2 and MMP-13 in the MSC group were significantly decreased compared to those in model group (P < 0.05). However, MMP2 and MMP13 in the siRNA-MSC group were not significantly decreased compared to the model group (P < 0.05). Magnetic resonance results revealed a significant improvement in cartilage and synovial membrane 4 weeks after MSC injection. Histopathology determination showed that cartilage structure was also significantly improved in MSC group. Immunohistochemical analysis revealed amelioration in the expression levels of proteoglycan, COL-2, P21 and P53 in MSC group. On the other hand, MRI, histopathologic and immunohistochemical analysis also indicated a decreased therapeutic effect with SOD-siRNA -MSC. The positive rate of β-galactosidase staining and ROS level of OA chondrocytes were significantly higher than those in normal chondrocytes, which was decreased in OA chondrocytes + MSC (P < 0.05). In addition, it was increased in OA chondrocytes + siRNA-MSC (P < 0.05). CONCLUSION: Our study demonstrated for the first time that MSC might be a promising therapy in OA through anti-apoptosis and regeneration in chondrocyte by secreting SOD and improving oxidative stress.