Receptor activator of NF-κB ligand (RANKL) is a key factor in osteoclast differentiation that induces changes in the chromatin state of osteoclast precursors. However, the epigenetic mechanisms that regulate osteoclast differentiation have not been well clarified. Park-Min et al. report that the benzodiazepine derivative, I-BET151, a small-molecule inhibitor of BET proteins (which bind to acetylated histones and control gene transcription), suppresses RANKL-induced osteoclastogenesis and prevents bone loss in several mouse disease models. I-BET151 was shown to target a MYC–nuclear factor of activated T cells (NFAT) axis important for osteoclastogenesis.
References
Park-Min, K.-H. et al. Inhibition of osteoclastogenesis and inflammatory bone resorption by targeting BET proteins and epigenetic regulation. Nature Comm. 5, 5418 (2014)
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Crunkhorn, S. BET inhibitor prevents bone loss. Nat Rev Drug Discov 14, 16 (2015). https://doi.org/10.1038/nrd4515
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DOI: https://doi.org/10.1038/nrd4515
