Superparamagnetic Iron Oxide Nanoparticles Activate Mitogen-Activated Protein Kinase Pathway and Promote Bone Marrow Derived Mesenchymal Stem Cells Homing to Repair Bone Defects in Rats with Osteosarcoma

Abstract

Superparamagnetic iron oxide nanoparticles exert its action on repairing bone defects. Whether they have the same repair effect on osteosarcoma bone defects and the mechanism is worth studying. The bone defect model of osteosarcoma rats was constructed and divided into bone defect group, positive control group, low-dose nano-group, medium-dose nano-group, high-dose nano-group, and blocker group followed by analysis of new bone formation, bone marrow derived mesenchymal stem cells (BMSC) homing, bone morphogenetic protein-2 (BMP-2), Collagen I, and Phosphorylated 44/42 mitogen-activated protein kinase (p44/42) protein expression. The proportion of new bone formation in positive control group and different dose groups was higher than bone defect group and blocker group (P <0.05). The positive control group had rich collagen fibers at repair site, which were more cellulose and neatly arranged. Low-dose group was more collagenous than positive control group. There was no new bone formation in the bone defect group and the blocking agent group and no Y chromosome positive cells were found in the blood vessel wall. New bone formation was seen in the positive control group and the nano-group and the number of blood vessels was abundant and rich in Y chromosome positive cells. Compared with the other two groups, positive control group and nano-group had higher BMP-2, Collagen I expression (P <0.05), and lower p44/42 expression (P <0.05). The p-mitogen-activated protein kinase (MAPK) levels were the lowest in bone defect group, blocker group, and positive control group, while nano-group was opposite. Superparamagnetic iron oxide nanoparticles can repair bone defects in osteosarcoma rats, and the mechanism of action is mainly related to the activation of the MAPK pathway.