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 C. Mansky

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19 Scopus citations


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
Issue number9
StatePublished - Sep 2017

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© 2017 Blixt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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