Abstract
Gene expressionis controlled by epigenetic mechanisms including histone methylation. Osteoclasts are bone-resorptive cells that differentiate from hematopoietic-precursor cells by receptor activator of nuclear factor-κB ligand (RANKL) stimulation. Although BIX01294, a specific inhibitor of G9a, which works as a histone H3 lysine 9 (H3K9) methyltransferase, reportedly changes cellular differentiational stage, its effect on osteoclast differentiation is unclear. In this study, the effects of BIX01294 on osteoclast differentiation were examined. Here, we showed that BIX01294 dose-dependently reduced RANKL-induced tartrate-resistant acid phosphatase positive multinuclear osteoclast-like cell differentiation from murine macrophage-like Raw264.7 cells. During differentiation, growth rates reduced only less than 14% of those of cells stimulated with RANKL alone by BIX01294 treatment. Moreover, western blot analysis showed that BIX01294 reduced RANKL-induced carbonic anhydrase II and cathepsin K production and decreased RANKL-induced nuclear factor of activated T-cell c1, a master regulatory transcription factor, production during osteoclast differentiation. These results suggest that BIX01294 suppresses RANKL-induced osteoclast differentiation. This is the first report about the effect of BIX01294 on osteoclast differentiation.
Highlights
Bone remodelling is a dynamic process performed by osteoblast and osteoclast
Multinuclear giant osteoclast cells are formed by the differentiation of hematopoietic precursor cells, which shear a common progenitor with macrophages and dendritic cells [ ]
We demonstrated the effect of H K methylation status on osteoclast differentiation by using BIX, a specific inhibitor of G a that methylates H K [ ]
Summary
Bone remodelling is a dynamic process performed by osteoblast and osteoclast. The balance between the amount of bone matrix produced by osteoblasts and bone resorption by osteoclasts is essential for proper bone metabolism. This process is tightly regulated by various hormones and cytokines in the local microenvironments, and its impairment can lead to bone diseases [ ]. Multinuclear giant osteoclast cells are formed by the differentiation of hematopoietic precursor cells, which shear a common progenitor with macrophages and dendritic cells [ ]. Osteoclasts secrete proton and extracellular matrix-digestive enzymes into the resorptive pit, subsequently resulting in bone resorption [ ]. An excessive number or an increased function of osteoclasts is responsible
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