The development of a new drug TNFα antagonistic peptide that inhibits bone destruction by cancer cells

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In previous studies, we have reported that TNFα antagonistic peptide (W9 peptide) inhibit in vitro osteoclast formation induced by RANKL and M-CSF in bone marrow cell culture derived from the TNF receptor KO mice. Furthermore, W9 peptide blocked RANKL induced signaling downstream of RANK. Because of these results, W9 peptide interfered with not only TNFα-TNF receptor interaction but also RANKL/RANK interaction.In this study, we confirmed the effects of W9 peptide on the various model mice in vivo. We investigated the effects of W9 peptide on the Collagen-Induced Arthritis (CIA) mice induced inflammatory bone resorption. W9 peptide injections inhibited both inflammation and bone resorption induced in the CIA mice. These results indicated that W9 peptide had an inhibitory effect on the inflammatory bone resorption. In addition, we also investigated whether W9 peptide inhibited bone destruction in periodontal pathogens infection in mice or not. W9 peptide treatment by infusion pumps preve … More nted bone resorption induced in the calvalia of periodontal pathogens infection mice. W9 peptide could inhibit the bone resorption by periodontal pathogens. These results suggested that W9 peptide acted as antagonist of the RANKL/RANK interaction in vivo.Recently, it is reported that cancer cells capable of the metastasis to the bone, such as breast, prostate, and lung cancer, accelerate osteoclast formation and differentiation in vitro. It is also reported that OPG and bisphosphonates treatments prevent bone destruction induced by the metastasis to the bone in mice. These results is suggested that osteoclasts have a pivotal role in bone destruction induced by the metastasis. Therefore, we suggest the possibility that W9 peptide, acted as the antagonist of the RANKL/RANK interaction, inhibits bone destruction by cancer cells.In conclusion, W9 peptide inhibited the inflammatory bone resorption in vivo and RANKL-induced signaling downstream of RANK in vitro, suggesting that W9 peptide is possibly useful for the treatment of bone destruction by the cancer cells. Less