Mechanisms underlying the regulation and functions of HDAC7 in osteoclast differentiation

Abstract

The purpose of this research is to characterize the regulation and functions of Histone Deacetylase 7 (HDAC7) in osteoclast differentiation. Histone Deacetylases (HDACs) are negative regulators of transcription.1 Endochondral bone formation including maturation of chondrocytes and osteoblasts is regulated by HDACs.2 It has been shown that the suppression of HDAC7 enhanced osteoclast formation while the overexpression of myc-HDAC7 inhibits osteoclast formation.3 Hence, it has been suggested that the stimulation of HDAC7 might be a unique therapeutic strategy to reduce osteoclastic bone loss.3 However, the mechanism and the molecular pathways regulating how HDAC7 inhibits osteoclast formations have not been examined. In this study, we hypothesized that the deacetylase catalytic activity of HDAC7 is necessary for suppression of osteoclast formation. It is also hypothesized that the subcellular localization of HDAC7 in nucleus facilitated by the phosphorylation of serine residues at N- terminal with Receptor activator of nuclear factor-kappaB ligand (RANKL) stimulation is the one of the mechanism that HDAC7 controls osteoclast differentiation. However, from this study, it is found that HDAC7 deacetylase activity is dispensable for HDAC7-mediated inhibition of osteoclastogenesis. It is also concluded that the presence of HDAC7, not necessarily the localization of HDAC7 in the nucleus, is necessary to repress the osteoclastogenesis.