{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T16:13:51Z","timestamp":1772208831180,"version":"3.50.1"},"reference-count":108,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,12,28]],"date-time":"2015-12-28T00:00:00Z","timestamp":1451260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Irish Endodontic Society","award":["2008\/1"],"award-info":[{"award-number":["2008\/1"]}]},{"name":"European Society of Endodontology","award":["ARG 2012\/2"],"award-info":[{"award-number":["ARG 2012\/2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Direct application of histone\u2010deacetylase\u2010inhibitors (HDACis) to dental pulp cells (DPCs) induces chromatin changes, promoting gene expression and cellular\u2010reparative events. We have previously demonstrated that HDACis (valproic acid, trichostatin A) increase mineralization in dental papillae\u2010derived cell\u2010lines and primary DPCs by stimulation of dentinogenic gene expression. Here, we investigated novel genes regulated by the HDACi, suberoylanilide hydroxamic acid (SAHA), to identify new pathways contributing to DPC differentiation. SAHA significantly compromised DPC viability only at relatively high concentrations (5\u2009\u03bcM); while low concentrations (1\u2009\u03bcM) SAHA did not increase apoptosis. HDACi\u2010exposure for 24\u2009h induced mineralization\u2010per\u2010cell dose\u2010dependently after 2 weeks; however, constant 14d SAHA\u2010exposure inhibited mineralization. Microarray analysis (24\u2009h and 14\u2009days) of SAHA exposed cultures highlighted that 764 transcripts showed a significant &gt;2.0\u2010fold change at 24\u2009h, which reduced to 36 genes at 14\u2009days. 59% of genes were down\u2010regulated at 24\u2009h and 36% at 14\u2009days, respectively. Pathway analysis indicated SAHA increased expression of members of the matrix metalloproteinase (MMP) family. Furthermore, SAHA\u2010supplementation increased MMP\u201013 protein expression (7\u2009d, 14\u2009days) and enzyme activity (48\u2009h, 14\u2009days). Selective MMP\u201013\u2010inhibition (MMP\u201013i) dose\u2010dependently accelerated mineralization in both SAHA\u2010treated and non\u2010treated cultures. MMP\u201013i\u2010supplementation promoted expression of several mineralization\u2010associated markers, however, HDACi\u2010induced cell migration and wound healing were impaired. Data demonstrate that short\u2010term low\u2010dose SAHA\u2010exposure promotes mineralization in DPCs by modulating gene pathways and tissue proteases. MMP\u201013i further increased mineralization\u2010associated events, but decreased HDACi cell migration indicating a specific role for MMP\u201013 in pulpal repair processes. Pharmacological inhibition of HDAC and MMP may provide novel insights into pulpal repair processes with significant translational benefit. J. Cell. Physiol. 231: 798\u2013816, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.25128","type":"journal-article","created":{"date-parts":[[2015,8,11]],"date-time":"2015-08-11T22:48:56Z","timestamp":1439333336000},"page":"798-816","source":"Crossref","is-referenced-by-count":36,"title":["The Histone\u2010Deacetylase\u2010Inhibitor Suberoylanilide Hydroxamic Acid Promotes Dental Pulp Repair Mechanisms Through Modulation of Matrix Metalloproteinase\u201013 Activity"],"prefix":"10.1002","volume":"231","author":[{"given":"Henry F.","family":"Duncan","sequence":"first","affiliation":[{"name":"Division of Restorative Dentistry and Periodontology Dublin Dental University Hospital, Trinity College Dublin Lincoln Place, Dublin 2 Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Oral Biology School of Dentistry University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Garry J. P.","family":"Fleming","sequence":"additional","affiliation":[{"name":"Material Science Unit Dublin Dental University Hospital, Trinity College Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola C.","family":"Partridge","sequence":"additional","affiliation":[{"name":"Department of Basic Science and Craniofacial Biology New York University College of Dentistry New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Basic Science and Craniofacial Biology New York University College of Dentistry New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary P.","family":"Moran","sequence":"additional","affiliation":[{"name":"Division of Oral Biosciences Dublin Dental University Hospital, Trinity College Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Oral Biology School of Dentistry University of Birmingham Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207678"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001150"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2133"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-8935-6-11"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27512"},{"key":"e_1_2_6_7_1","first-page":"909","article-title":"Efficacy of MS\u2010275, a selective inhibitor of class I histone deacetylases, in human colon cancer models","volume":"35","author":"Bracker TU","year":"2009","journal-title":"Int J Oncol"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v21.i2.10"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.10.031"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20544"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.12.2927"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009080851"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.489732"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034511406919"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2011.12.014"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.02.022"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.4.879"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.233"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.602763"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404493"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4453"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2012.0711"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2227"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.02.006"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2004.02.002"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1467506"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016350600963640"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.081080"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407788101"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2012.0163"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkr1074"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070779"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-0920-9"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i6.813"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2008.03.020"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512443367"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-2-67"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.490706"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058267"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.142141"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.27.1497"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00051.2013"},{"key":"e_1_2_6_43_1","first-page":"113","article-title":"Butyrate Induced cell cycle arrest in bovine cells through targeting gene expression relevant to DNA replication apparatus","volume":"2","author":"Li CJ","year":"2008","journal-title":"Gene Regul Syst Biol"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-005-9005-2"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0633"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/284067a0"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.05.643"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.01.007"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2010.12.003"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2013.12.562"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-13-709"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.14.12.1497"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.22185"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2010.05.008"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211695200"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2008.04.022"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2004.07.001"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-3531"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199809000-00011"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2006.09.013"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1042\/BC20090122"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgl167"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21491"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.013631"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.337063"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01176.x"},{"key":"e_1_2_6_67_1","first-page":"205","article-title":"Systemic cell\u2010cycle suppression by Apicidin, a histone deacetylase inhibitor, in MDA\u2010MB\u2010435","volume":"24","author":"Noh JH","year":"2009","journal-title":"Int J Mol Med"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M605370200"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb03214.x"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1544"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.07.034"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0722.2003.00026.x"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2009.06.008"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3517"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705867200"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-007-9751-0"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.52.37292"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000553"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.01.152"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1177\/002203458506400407"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.050813"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-8-362"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.094862"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450111009011430"},{"key":"e_1_2_6_85_1","first-page":"273","article-title":"Reactionary dentinogenesis","volume":"39","author":"Smith AJ","year":"1995","journal-title":"Int J Dev Biol"},{"key":"e_1_2_6_86_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.12968\/denu.2002.29.2.64","article-title":"Preserving the vital pulp in operative dentistry: 1. A biological approach","volume":"29","author":"Smith AJ","year":"2002","journal-title":"Dent Update"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-008-0189-5"},{"key":"e_1_2_6_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2012.07.008"},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.4161\/cib.25466"},{"key":"e_1_2_6_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-013-0493-2"},{"key":"e_1_2_6_91_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008200490885788"},{"key":"e_1_2_6_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2008.02.010"},{"key":"e_1_2_6_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng892"},{"key":"e_1_2_6_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdent.2007.04.008"},{"key":"e_1_2_6_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700500"},{"key":"e_1_2_6_96_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0896"},{"key":"e_1_2_6_97_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-399"},{"key":"e_1_2_6_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(03)00073-8"},{"key":"e_1_2_6_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.01.011"},{"key":"e_1_2_6_100_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1673"},{"key":"e_1_2_6_101_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199912)181:3<479::AID-JCP12>3.0.CO;2-D"},{"key":"e_1_2_6_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(01)00192-5"},{"key":"e_1_2_6_103_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.4.639"},{"key":"e_1_2_6_104_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25061"},{"key":"e_1_2_6_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2012.182"},{"key":"e_1_2_6_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(99)00157-X"},{"key":"e_1_2_6_107_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345960750081101"},{"key":"e_1_2_6_108_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvs117"},{"key":"e_1_2_6_109_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12043"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.25128","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.25128","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.25128","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T05:57:20Z","timestamp":1696399040000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.25128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,28]]},"references-count":108,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1002\/jcp.25128"],"URL":"https:\/\/doi.org\/10.1002\/jcp.25128","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,28]]}}}