Local administration of WP9QY (W9) peptide promotes bone formation in a rat femur delayed-union model

The WP9QY peptide (W9) consists of nine amino acids. It binds to RANKL and blocks RANKL-induced increases in bone resorption and osteoclastogenesis. W9 has a unique effect on the coupling mechanism between osteoclasts and osteoblasts, which promotes bone formation while working to suppress bone resorption. In this study, with the aim of clinical application of W9 for fracture treatment, we aimed to clarify the bone repair-promoting effect of W9 when administered locally to a rat femur model of delayed union. Using Sprague-Dawley rats, a model of delayed union was created in the right femur by cauterizing the periosteum. Injection of W9 (1 mg in 100 mu l) or phosphate-buffered saline (PBS) (100 mu l) at the fracture site was performed at the operation and every week thereafter until death (sacrifice). The bone union rate was 14% in the PBS group and 57% in the W9 group at 8 weeks postoperatively. The X-ray score of the W9 group was significantly higher than that of the PBS group at 8 weeks postoperatively. When bone morphometry was analyzed by micro-computed tomography (CT), total callus volume (TV) and mineralized callus bone volume (BV) were measured. TV showed no significant difference between the two groups, but BV/TV was significantly higher in the W9 group. This finding suggests that local administration of W9 can promote bone maturation from callus and can be considered to contribute to fracture healing. These results reveal that W9 has an effect on fractures of promoting healing and could be applied as a fracture treatment.