S100A4 has been shown to utilize cell surface receptors, including RAGE, TLR4, CD44, and annexin 2, in diverse cell types.32 In particular, RAGE has been implicated in the metastasis of several types of cancers, including lung, brain, and prostate cancer and osteosarcoma.33–35 Here we demonstrated that RAGE served as the receptor for S100A4 in stimulating osteoclastogenesis. Here, TLR4 is linked to cancer.