The small molecule harmine regulates NFATc1 and Id2 expression in osteoclast progenitor cells

► An osteoclast progenitor cell-based high-throughput screening system was designed. ► Orphan ligand library screening identified harmine to be an NFAT-targeting molecule. ► Harmine activated NFATc1 expression by interfering with DYRK1A in preosteoclasts. ► Harmine induced Id2 expression leading to dominant inhibition of cell-cell fusion.