Bone Abstracts

Osteoclasts are bone-resorbing multinucleated cells that differentiate from monocyte/macrophage-lineage precursors. Bone destruction and osteoporosis are attributed to excessively activated osteoclasts. Osteoclast differentiation is governed by diverse regulatory processes including nuclear factor-activated T cells c1 (NFATc1) activation in response to RANKL. The mechanism of epigenetic regulation of NFATc1 in osteoclastogenesis not investigated yet. Here we test a hypothesis that a jumonji histone demethylase might epigenetically regulate NFATc1 during osteoclast differentiation. Western blot analysis showed decrease of jumonji histone demethylase expression during osteoclastogenesis of RAW264.7 cell line. The knock down expression of a jumonji histone demethylase in RAW264.7 and bone marrow macrophages facilitated the osteoclastogenesis through RANKL. Luciferase reporter assay showed that the suppression of a jumonji histone demethylase also increased the transcriptional activity of NFATc1. Immunoprecipitation assay showed that a jumonji histone demethylase directly binds to the C-terminal of NFATc1. From the above results, I suggest that a jumonji histone demethylase plays a suppressive role in osteoclastogenesis. As for part of the signaling mechanisms of the inhibition of transcriptional activity, direct protein–protein interaction between a jumonji histone demethylase and NFATc1 was suggested.