A Crucial Role of IL-17 in Bone Resorption During Rejection of Fresh Bone Xenotransplantation in Rats

Bone grafting is a very useful approach to reconstruction of skeletal defects. However, the clinical use of autografts, allografts, and synthetic products is associated with a number of problems. The use of bone xenotransplantation, on the other hand, is associated with strong immune response, and therefore clear understanding of the mechanisms of immune rejection is essential. In this study, we used rabbit-to-rat xenotransplantation model to investigate the role of IL-17, and the relationship between IL-17, IL-23 and RANKL in inflammatory response during the bone grafting. Rabbit hindlimb bone was transplanted to rats, and half of the xenograft recipient animals received injection of IL-17 neutralizing antibodies before xenotransplantation. Sham control rats did not receive bone transplants. In the xenotransplant group, significant mononuclear cell infiltration and erosion/resorption of graft bone were observed. Administration of IL-17 neutralizing antibodies decreased mononuclear cell infiltration and inhibited bone resorption. The levels of IL-17+, IL-23+, and RANKL+ cells were elevated in xenotransplanted group from compared to the sham control. IL-17+ and RANKL+ cells infiltration was decreased upon administration of IL-17 neutralizing antibodies. No significant difference in the level of IL-23 in xenotransplanted groups with and without IL-17 antibodies was observed. Our results indicate that RANKL, IL-17, and IL-23 participate in the immune rejection of bone xenotransplantion. The IL-17/RANKL pathway may play a very important role in the bone resorption during rejection of fresh bone xenotransplants.