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  • Title: Inhibitory effect of cantharidin on osteoclast differentiation and bone resorption.
    Author: Kim MH, Shim KS, Kim SH.
    Journal: Arch Pharm Res; 2010 Mar; 33(3):457-62. PubMed ID: 20361312.
    Abstract:
    Regulation of receptor activator of nuclear factor kappaB-ligand (RANKL)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. We identified the inhibitory effects of cantharidin on RANKL-induced differentiation and bone resorptive activities of osteoclasts in macrophage-like RAW264.7 cells. Interestingly, cantharidin significantly inhibited RANKL-induced ERK/MAP kinase activation and protein phosphatase 2A (PP2A) activity. In addition, cantharidin significantly inhibited RANKL-induced mRNA expression of transcription factors and osteoclast-specific genes (especially Fra-2 and cathepsin K, respectively). Although further studies might be required to elucidate the precise mechanism of cantharidin's action on osteoclast differentiation and bone resorptive activities, our results suggested that cantharidin-mediated inactivation of PP2A could prevent RANKLinduced activation of ERK/MAP kinase and transcription factors such as AP-1 and NFATc1, with subsequent inhibition of osteoclast-specific gene expression required for efficient osteoclast differentiation and bone resorption.
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