title: Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF.
abstract: Molecular regulators of osteoclast formation and function are an important area of research due to the central role of osteoclasts in bone resorption. Transcription factors such as MITF are essential for osteoclast generation by regulating expression of the genes required for cellular differentiation and resorptive function. We recently reported that histone deacetylase 7 (HDAC7) binds to and represses the transcriptional activity of MITF in osteoclasts, and that loss of HDAC7 in vitro accelerated osteoclastogenesis. In the current study, we extend this initial observation by showing that conditional deletion of HDAC7 in osteoclasts of mice leads to an in vivo enhancement in osteoclast formation, associated with increased bone resorption and lower bone mass. Expression of multiple MITF target genes is increased in bone marrow derived osteoclast cultures from the HDAC7 knockout mice. Interestingly, multiple regions of the HDAC7 amino-terminus can bind to MITF or exert repressive activity. Moreover, mutation or deletion of the HDAC7 conserved deacetylase catalytic domain had little effect on repressive function. These observations identify HDAC7 in osteoclasts as an important molecular regulator of MITF activity and bone homeostasis, but also highlight a gap in our understanding of exactly how HDAC7 functions as a corepressor.
authors: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Melissa
authors: M
authors: Stemig
authors: Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Kristina
authors: K
authors: Astelford
authors: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Ann
authors: A
authors: Emery
authors: Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Jangyeun J
authors: JJ
authors: Cho
authors: Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Ben
authors: B
authors: Allen
authors: Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Tainan City, 701, Taiwan.
authors: Tsang-hai
authors: TH
authors: Huang
authors: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Rajaram
authors: R
authors: Gopalakrishnan
authors: Department of Developmental and Surgical Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Kim C
authors: KC
authors: Mansky
authors: Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors: Eric D
authors: ED
authors: Jensen
mesh_terms: D000818:Animals; D015519:Bone Density / Q000235:genetics*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001862:Bone Resorption / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020134:Catalytic Domain; D002454:Cell Differentiation; D005260:Female; D005269:Femur / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C543274:Hdac7 protein, mouse; D006655:Histone Deacetylases