Class II and IV HDACs function as inhibitors of osteoclast differentiation

Nicholas C. Blixt, Bora K. Faulkner, Kristina Astleford, Rosemary Lelich, Jacob Schering, Ekaterina Spencer, Rajaram Gopalakrishnan, Eric D Jensen, Kim Mansky

Research output: Contribution to journalArticle

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Abstract

Histone deacetylases (HDACs) are negative regulators of transcription and have been shown to regulate specific changes in gene expression. In vertebrates, eighteen HDACs have thus far been identified and subdivided into four classes (I-IV). Key roles for several HDACs in bone development and biology have been elucidated through in vitro and in vivo models. By comparison, there is a paucity of data on the roles of individual HDACs in osteoclast formation and function. In this study, we investigated the gene expression patterns and the effects of suppressing individual class II (Hdac4, 5, 6, 9, and 10) and class IV (Hdac11) HDACs during osteoclast differentiation. We demonstrated that HDAC class II and IV members are differentially expressed during osteoclast differentiation. Additionally, individual shRNA-mediated suppression of Hdac4, 5, 9, 10 and 11 expression resulted in increased multinucleated osteoclast size and demineralization activity, with little to no change in the overall number of multinucleated osteoclasts formed compared with control shRNA-treated cells. We also detected increased expression of genes highly expressed in osteoclasts, including c-Fos, Nfatc1, Dc-stamp and Cathepsin K. These observations indicate that HDACs cooperatively regulate shared targets in a non-redundant manner.

Original languageEnglish (US)
Article numbere0185441
JournalPLoS One
Volume12
Issue number9
DOIs
StatePublished - Sep 1 2017

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osteoclasts
Histone Deacetylases
Osteoclasts
histones
Gene Expression
Gene expression
gene expression
Small Interfering RNA
cathepsin K
Cathepsin K
skeletal development
Bone Development
Transcription
Vertebrates
Bone
transcription factors
Genes
vertebrates
Cells
Biological Sciences

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Blixt, N. C., Faulkner, B. K., Astleford, K., Lelich, R., Schering, J., Spencer, E., ... Mansky, K. (2017). Class II and IV HDACs function as inhibitors of osteoclast differentiation. PLoS One, 12(9), [e0185441]. https://doi.org/10.1371/journal.pone.0185441

Class II and IV HDACs function as inhibitors of osteoclast differentiation. / Blixt, Nicholas C.; Faulkner, Bora K.; Astleford, Kristina; Lelich, Rosemary; Schering, Jacob; Spencer, Ekaterina; Gopalakrishnan, Rajaram; Jensen, Eric D; Mansky, Kim.

In: PLoS One, Vol. 12, No. 9, e0185441, 01.09.2017.

Research output: Contribution to journalArticle

Blixt NC, Faulkner BK, Astleford K, Lelich R, Schering J, Spencer E et al. Class II and IV HDACs function as inhibitors of osteoclast differentiation. PLoS One. 2017 Sep 1;12(9). e0185441. https://doi.org/10.1371/journal.pone.0185441
Blixt, Nicholas C. ; Faulkner, Bora K. ; Astleford, Kristina ; Lelich, Rosemary ; Schering, Jacob ; Spencer, Ekaterina ; Gopalakrishnan, Rajaram ; Jensen, Eric D ; Mansky, Kim. / Class II and IV HDACs function as inhibitors of osteoclast differentiation. In: PLoS One. 2017 ; Vol. 12, No. 9.
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