Surprisingly, very few transcription factors have been implicated in osteoclast differentiation. Newly discovered upregulated transcription factors are obviously important in understanding osteoclast differentiation. However, we speculate that repression of transcription factor genes may also be necessary for osteoclast differentiation. In particular, we have looked for differential regulation of transcription factors between the two alternative states: macrophage and osteoclast. Two recent papers verified the role of NFATc1 in osteoclastogenesis [1,2]; NFATc1 is required for the production of TRAP positive multinucleated osteoclast like cells (OCLs). We show here that NFATc1 and other transcription factors are strongly induced by RANKL in human osteoclast like cells. NFATc1 regulation steadily increases across time with a peak of 26 fold at three weeks post treatment with macrophage colony stimulating factor (M-CSF) and RANKL. Along with NFATc1 we have observed significant up-regulation of four other transcription factors: GA-binding protein a and b (GABP), early response growth factor 1 (EGR-1), and FUSE binding protein (FBP). The dynamics of regulation of ERG-1 and GABPa and b were identical to that of NFATc1. However FBP regulation peaks earlier and is of great magnitude. These data show that NFATc1 is not the only strongly regulated transcription factor in osteoclast differentiation and is later induced than FBP.