Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF.
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 differentiatio...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4398560?pdf=render |
| _version_ | 1818479430480166912 |
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| author | Melissa Stemig Kristina Astelford Ann Emery Jangyeun J Cho Ben Allen Tsang-hai Huang Rajaram Gopalakrishnan Kim C Mansky Eric D Jensen |
| author_facet | Melissa Stemig Kristina Astelford Ann Emery Jangyeun J Cho Ben Allen Tsang-hai Huang Rajaram Gopalakrishnan Kim C Mansky Eric D Jensen |
| author_sort | Melissa Stemig |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T11:10:29Z |
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| id | doaj.art-c9330c59394a4c3aa5ff25b5b41f8c85 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T11:10:29Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-c9330c59394a4c3aa5ff25b5b41f8c852022-12-22T01:51:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012384310.1371/journal.pone.0123843Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF.Melissa StemigKristina AstelfordAnn EmeryJangyeun J ChoBen AllenTsang-hai HuangRajaram GopalakrishnanKim C ManskyEric D JensenMolecular 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.http://europepmc.org/articles/PMC4398560?pdf=render |
| spellingShingle | Melissa Stemig Kristina Astelford Ann Emery Jangyeun J Cho Ben Allen Tsang-hai Huang Rajaram Gopalakrishnan Kim C Mansky Eric D Jensen Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF. PLoS ONE |
| title | Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF. |
| title_full | Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF. |
| title_fullStr | Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF. |
| title_full_unstemmed | Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF. |
| title_short | Deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with MITF. |
| title_sort | deletion of histone deacetylase 7 in osteoclasts decreases bone mass in mice by interactions with mitf |
| url | http://europepmc.org/articles/PMC4398560?pdf=render |
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