Mesenchymal stem cells improve osteoarthritis by secreting superoxide dismutase to regulate oxidative stress response

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).

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.

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).

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.