The effects of RANKL antagonist peptide on bone formation

Objectives: W9 peptide is known to attenuate inflammatory bone resorption by antagonizing the actions of both TNF (tumor necrosis factor)-α and RANKL (receptor activator of NF κ B ligand). It has already been shown that W9 peptide can inhibit the bone destruction in various bone resorption models. However, the effects of W9 peptide on bone formation have not been elucidated yet. The purpose of the study was to investigate the effects of W9 peptide on bone formation. Methods: Five week`s old C57BL/6 mice were used in this study. First, we injected W9 peptide 10 mg/kg or vehicle (10% DMSO) 3 times/day for 5 days. Mice were sacrificed on the next day. Radiological analysis of the bone was performed. To induce ectopic bone, we implanted collagen disc containing 2 μgram BMP alone as a control or combine with W9 peptide (1.12 mg and 0.56 mg). Mice were sacrificed on day 12 and the ectopic bone formation was analyzed.Results: pQCT analysis showed that the 5 day`s injection (3 times/day) of W9 peptide increased cortical thickness, trabecular density, strength strain index of femur significantly compare to the vehicle injection. Mineral apposition rate was significantly increased by W9 peptide injection. In the ectopic bone formation experiment, radio opacities of ectopic bone compared to the BMP alone was increased by W9 peptide. Dual energy X-ray absorptiometry revealed bone mineral content of the ectopic bone with 0.56 mg W9 peptide was bigger than control by 2.35 times and with 1.12 mg W9 by 1.82 times. Conclusion: Our finding suggests that W9 peptide might promote bone formation and has additive effect on ectopic bone formation induced by BMP.