Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/119902
Citations
Scopus Web of Science® Altmetric
?
?
Full metadata record
DC FieldValueLanguage
dc.contributor.authorAlgate, K.en
dc.contributor.authorHaynes, D.en
dc.contributor.authorFitzsimmons, T.en
dc.contributor.authorRomeo, O.en
dc.contributor.authorWagner, F.en
dc.contributor.authorHolson, E.en
dc.contributor.authorReid, R.en
dc.contributor.authorFairlie, D.en
dc.contributor.authorBartold, P.en
dc.contributor.authorCantley, M.en
dc.date.issued2020en
dc.identifier.citationJournal of Cellular Biochemistry, 2020; 121(1):244-258en
dc.identifier.issn0730-2312en
dc.identifier.issn1097-4644en
dc.identifier.urihttp://hdl.handle.net/2440/119902-
dc.descriptionFirst published: 21 June 2019en
dc.description.abstractThe regulation of epigenetic factors is an emerging therapeutic target of immune function in a variety of osteolytic pathologies. Histone deacetylases (HDAC) modify core histone proteins and transcriptional processes, in addition to nonhistone protein activity. The activated immune response in rheumatoid arthritis, periodontitis, and prosthetic implant particle release stimulates the catabolic activity of osteoclasts. In this study, we investigated the effects of novel therapeutic agents targeting HDAC isozymes (HDAC 1, 2, and 5), previously shown to be upregulated in inflammatory bone disorders, in cytokine-stimulated human monocytes and osteoclasts in vitro. Inhibiting HDAC 1 and 2 significantly reduced gene expression of IL-1β, TNF, MCP-1, and MIP-1α in TNF-stimulated monocytes, while suppressing secretions of IL-1β, IL-10, INF-γ, and MCP-1 (P < .05). Osteoclast formation and bone resorption were also significantly diminished with HDAC 1 and 2 inhibition, through reduced NFATc1 expression and osteoclast specific target genes, TRAF6, CTR, TRAP, and Cathepsin K (P < .05). Similar trends were observed when inhibiting HDAC 1 and to a lesser extent, HDAC 2, in isolation. However, their combined inhibition had the greatest anti-inflammatory and antiosteoclastic effects. Targeting HDAC 5 had minimal effects on these processes investigated in this study, whereas a broad acting HDACi, 1179.4b, had widespread suppressive outcomes. This study demonstrates that targeting HDACs is a potent and effective way of regulating the inflammatory and catabolic processes in human monocytes and osteoclasts. It also demonstrates the importance of targeting individual HDACs with an overall aim to improve efficiency and reduce any potential off target effects.en
dc.description.statementofresponsibilityKent Algate, David Haynes, Tracy Fitzsimmons, Ornella Romeo, Florence Wagner, Edward Holson, Robert Reid, David Fairlie, Peter Bartold, Melissa Cantleyen
dc.language.isoenen
dc.publisherWileyen
dc.rights© 2019 Wiley Periodicals, Inc.en
dc.subjectbone loss; epigenetics; histone deacetylases (HDAC); inflammation; osteoclasts; tumor necrosis factor (TNF)en
dc.titleHistone deacetylases 1 and 2 inhibition suppresses cytokine production and osteoclast bone resorption in vitroen
dc.typeJournal articleen
dc.identifier.rmid0030119435en
dc.identifier.doi10.1002/jcb.29137en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1070880en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1057835en
dc.identifier.pubid479010-
pubs.library.collectionBiochemistry publicationsen
pubs.library.teamDS10en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidAlgate, K. [0000-0002-0224-5322]en
dc.identifier.orcidFitzsimmons, T. [0000-0002-1029-8352]en
dc.identifier.orcidBartold, P. [0000-0002-5695-3877]en
dc.identifier.orcidCantley, M. [0000-0002-7188-0928]en
Appears in Collections:Biochemistry publications

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.