title: HDAC3 and HDAC7 have opposite effects on osteoclast differentiation.
abstract: Histone deacetylases (HDACs) are negative regulators of transcription. Endochondral bone formation including chondrocyte and osteoblast maturation is regulated by HDACs. Very little is known about the role HDACs play in osteoclast differentiation. It has been previously reported that HDAC inhibitors, trichostatin A and sodium butyrate, suppress osteoclast differentiation through multiple mechanisms. In this study, we report that suppression of HDAC3 expression similar to HDAC inhibitors inhibits osteoclast differentiation, whereas osteoclasts suppressed for HDAC7 expression had accelerated differentiation when compared with control cells. Mitf, a transcription factor, is necessary for osteoclast differentiation. We demonstrate that Mitf and HDAC7 interact in RAW 264 cells and osteoclasts. The transcriptional activity of Mitf is repressed by HDAC7. Lastly, we show that either the amino or the carboxyl terminus of HDAC7 is sufficient for transcriptional repression and that the repression of HDAC7 is insensitive to trichostatin A, indicating that HDAC7 represses Mitf at least in part by deacetylation-independent mechanism.
authors.affiliation: Department of Developmental and Surgical Science, University of Minnesota School of Dentistry, Minneapolis, MN 55455, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Pham
authors.forename: Bria
authors.initials: B
authors.lastname: Kaiser
authors.forename: Amanda
authors.initials: A
authors.lastname: Romsa
authors.forename: Toni
authors.initials: T
authors.lastname: Schwarz
authors.forename: Raj
authors.initials: R
authors.lastname: Gopalakrishnan
authors.forename: Eric D
authors.initials: ED
authors.lastname: Jensen
authors.forename: Kim C
authors.initials: KC
authors.lastname: Mansky
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099186:Histone Deacetylase 3
chemical_list: D006655:Histone Deacetylases; D051739:Microphthalmia-Associated Transcription Factor; D000099186:Histone Deacetylase 3; C497235:Mitf protein, mouse; C543274:Hdac7 protein, mouse