{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:01:50Z","timestamp":1791489710755,"version":"4.3.4"},"reference-count":39,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470966"],"award-info":[{"award-number":["82470966"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["LCB202416"],"award-info":[{"award-number":["LCB202416"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7242140"],"award-info":[{"award-number":["7242140"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Dental Journal"],"published-print":{"date-parts":[[2025,8]]},"DOI":"10.1016\/j.identj.2025.100850","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T11:53:54Z","timestamp":1749470034000},"page":"100850","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["VPA Enhances Pulp Regeneration by Regulating LPS-Induced Human Dental Pulp Stem Cells Odontogenic Differentiation"],"prefix":"10.1016","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3666-3995","authenticated-orcid":false,"given":"Zhihua","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4190-030X","authenticated-orcid":false,"given":"Yi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomiao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkai","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaogang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxiong","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoru","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1305-7287","authenticated-orcid":false,"given":"Paul R.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1898-5480","authenticated-orcid":false,"given":"Shengchao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6841-5021","authenticated-orcid":false,"given":"Wenxi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.identj.2025.100850_bib0001","first-page":"33","article-title":"Dental pulp stem cells: advances to applications","volume":"13","author":"Tsutsui","year":"2020","journal-title":"Stem Cells Cloning"},{"issue":"9S","key":"10.1016\/j.identj.2025.100850_bib0002","doi-asserted-by":"crossref","first-page":"S46","DOI":"10.1016\/j.joen.2020.06.027","article-title":"Dental pulp stem cells: from discovery to clinical application","volume":"46","author":"Sui","year":"2020","journal-title":"J Endod"},{"key":"10.1016\/j.identj.2025.100850_bib0003","doi-asserted-by":"crossref","first-page":"108","DOI":"10.22203\/eCM.v041a08","article-title":"Liposomes embedded with differentiating factors as a new strategy for enhancing DPSC osteogenic commitment","volume":"41","author":"Gallorini","year":"2021","journal-title":"EUR CELLS MATER"},{"issue":"2","key":"10.1016\/j.identj.2025.100850_bib0004","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3390\/dj4020008","article-title":"Dental Pulp Stem Cell Recruitment Signals within Injured Dental Pulp Tissue","volume":"4","author":"Rombouts","year":"2016","journal-title":"Dentistry journal"},{"key":"10.1016\/j.identj.2025.100850_bib0005","doi-asserted-by":"crossref","first-page":"4894","DOI":"10.1038\/s41598-022-08835-4","article-title":"Comparison of GentleWave system and passive ultrasonic irrigation with minimally invasive and conventional instrumentation against LPS in infected root canals","volume":"12","author":"Velardi","year":"2022","journal-title":"Sci. Rep"},{"key":"10.1016\/j.identj.2025.100850_bib0006","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/s41598-022-26855-y","article-title":"Comparison of conventional and contemporary root canal disinfection protocols against bacteria, lipoteichoic acid (LTA), and lipopolysaccharide (LPS)","volume":"13","author":"Alquria","year":"2023","journal-title":"Sci. Rep"},{"key":"10.1016\/j.identj.2025.100850_bib0007","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.dental.2022.03.008","article-title":"Influence of HEMA on LPS- and LTA-stimulated IL-6 release from human dental pulp cells","volume":"38","author":"Schweikl","year":"2022","journal-title":"Dent Mater"},{"key":"10.1016\/j.identj.2025.100850_bib0008","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/j.1365-2591.2012.02096.x","article-title":"LPS induces IL-8 expression through TLR4, MyD88, NF-kappaB and MAPK pathways in human dental pulp stem cells","volume":"46","author":"He","year":"2013","journal-title":"Int Endod J"},{"key":"10.1016\/j.identj.2025.100850_bib0009","doi-asserted-by":"crossref","DOI":"10.1111\/cpr.13093","article-title":"Dental pulp stem cell-derived exosomes alleviate cerebral ischaemia-reperfusion injury through suppressing inflammatory response","volume":"54","author":"Li","year":"2021","journal-title":"Cell Prolif"},{"key":"10.1016\/j.identj.2025.100850_bib0010","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.jdent.2014.07.007","article-title":"The effects of LPS on adhesion and migration of human dental pulp stem cells in vitro","volume":"42","author":"Li","year":"2014","journal-title":"J Dent"},{"key":"10.1016\/j.identj.2025.100850_bib0011","article-title":"IFN-\u03b3 regulates human dental pulp stem cells behavior via NF-\u03baB and MAPK signaling","volume":"7","author":"He","year":"2017","journal-title":"Sci. Rep"},{"key":"10.1016\/j.identj.2025.100850_bib0012","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1089\/ten.tea.2012.0163","article-title":"HDAC inhibitor trichostatin A promotes proliferation and odontoblast differentiation of human dental pulp stem cells","volume":"19","author":"Jin","year":"2013","journal-title":"Tissue Eng Pt A"},{"key":"10.1016\/j.identj.2025.100850_bib0013","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s12938-017-0423-y","article-title":"Differentiation of human adipose-derived stem cells into cardiomyocyte-like cells in fibrin scaffold by a histone deacetylase inhibitor","volume":"16","author":"Bagheri-Hosseinabadi","year":"2017","journal-title":"Biomed Eng Online"},{"key":"10.1016\/j.identj.2025.100850_bib0014","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/bies.201000033","article-title":"Returning to the stem state: epigenetics of recapitulating pre-differentiation chromatin structure","volume":"32","author":"Shafa","year":"2010","journal-title":"BioEssays"},{"key":"10.1016\/j.identj.2025.100850_bib0015","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.3390\/cimb45030136","article-title":"Epigenetic modification of mesenchymal stromal cells derived from bone marrow and embryonal tumors to facilitate immunotherapeutic approaches in pediatric malignancies","volume":"45","author":"Kruchen","year":"2023","journal-title":"Curr Issues Mol Biol"},{"key":"10.1016\/j.identj.2025.100850_bib0016","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/iej.12779","article-title":"Effects of histone deacetylase inhibitors on regenerative cell responses in human dental pulp cells","volume":"51","author":"Luo","year":"2018","journal-title":"Int Endod J"},{"key":"10.1016\/j.identj.2025.100850_bib0017","doi-asserted-by":"crossref","first-page":"6969","DOI":"10.1093\/emboj\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells","volume":"20","author":"G\u00f6ttlicher","year":"2001","journal-title":"EMBO J"},{"key":"10.1016\/j.identj.2025.100850_bib0018","doi-asserted-by":"crossref","first-page":"669","DOI":"10.2165\/00023210-200216100-00003","article-title":"Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy","volume":"16","author":"L\u00f6scher","year":"2002","journal-title":"CNS Drugs"},{"key":"10.1016\/j.identj.2025.100850_bib0019","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrd2133","article-title":"Anticancer activities of histone deacetylase inhibitors","volume":"5","author":"Bolden","year":"2006","journal-title":"Nat. Rev. Drug Discovery"},{"key":"10.1016\/j.identj.2025.100850_bib0020","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1038\/cti.2015.46","article-title":"Histone deacetylases in monocyte\/macrophage development, activation and metabolism: refining HDAC targets for inflammatory and infectious diseases","volume":"5","author":"Gupta","year":"2016","journal-title":"Clin Transl Immunol"},{"key":"10.1016\/j.identj.2025.100850_bib0021","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/stem.1544","article-title":"Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: evidence for HDAC2 involvement","volume":"32","author":"Paino","year":"2014","journal-title":"Stem Cells"},{"key":"10.1016\/j.identj.2025.100850_bib0022","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.bonr.2017.08.001","article-title":"Histone deacetylases and their roles in mineralized tissue regeneration","volume":"7","author":"Huynh","year":"2017","journal-title":"Bone Rep"},{"key":"10.1016\/j.identj.2025.100850_bib0023","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.joen.2011.12.014","article-title":"Histone deacetylase inhibitors induced differentiation and accelerated mineralization of pulp-derived cells","volume":"38","author":"Duncan","year":"2012","journal-title":"J Endod"},{"key":"10.1016\/j.identj.2025.100850_bib0024","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/j.yexcr.2013.02.022","article-title":"Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells","volume":"319","author":"Duncan","year":"2013","journal-title":"Exp. Cell Res"},{"key":"10.1016\/j.identj.2025.100850_bib0025","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/s13287-022-02971-4","article-title":"Amphiregulin regulates odontogenic differentiation of dental pulp stem cells by activation of mitogen-activated protein kinase and the phosphatidylinositol 3-kinase signaling pathways","volume":"13","author":"Li","year":"2022","journal-title":"Stem Cell Res. Ther"},{"key":"10.1016\/j.identj.2025.100850_bib0026","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s13287-021-02349-y","article-title":"DPSCs treated by TGF-\u03b21 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2 signaling","volume":"12","author":"Zhang","year":"2021","journal-title":"Stem Cell Res. Ther"},{"key":"10.1016\/j.identj.2025.100850_bib0027","doi-asserted-by":"crossref","DOI":"10.1590\/S1678-77572009000300001","article-title":"Understanding dental pulp innate immunity\u2013a basis for identifying new targets for therapeutic agents that dampen inflammation","volume":"17","author":"Farges","year":"2009","journal-title":"J Appl Oral Sci"},{"key":"10.1016\/j.identj.2025.100850_bib0028","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jdsr.2018.03.001","article-title":"The roles of odontoblasts in dental pulp innate immunity","volume":"54","author":"Yumoto","year":"2018","journal-title":"Jpn Dent Sci Rev"},{"key":"10.1016\/j.identj.2025.100850_bib0029","first-page":"303","article-title":"The role of cytokines in pulp inflammation","volume":"25","author":"Kokkas","year":"2011","journal-title":"J Biol Regul Homeost Agents"},{"key":"10.1016\/j.identj.2025.100850_bib0030","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.joen.2014.03.015","article-title":"TLR4 activation by lipopolysaccharide and Streptococcus mutans induces differential regulation of proliferation and migration in human dental pulp stem cells","volume":"40","author":"Liu","year":"2014","journal-title":"J Endod"},{"key":"10.1016\/j.identj.2025.100850_bib0031","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22168991","article-title":"Functional Dental Pulp Regeneration: Basic Research and Clinical Translation","volume":"22","author":"Xie","year":"2021","journal-title":"Int. J. Mol. Sci"},{"issue":"3","key":"10.1016\/j.identj.2025.100850_bib0032","first-page":"253","article-title":"Regeneration potential of the young permanent tooth: what does the future hold?","volume":"30","author":"Hargreaves","year":"2008","journal-title":"Pediatr Dent"},{"key":"10.1016\/j.identj.2025.100850_bib0033","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.bbagrm.2010.05.008","article-title":"Histone deacetylase inhibitors: a chemical genetics approach to understanding cellular functions","volume":"1799","author":"Marks","year":"2010","journal-title":"Biochim. Biophys, Acta"},{"key":"10.1016\/j.identj.2025.100850_bib0034","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1111\/odi.14491","article-title":"Epigenetic regulation of osteogenic differentiation of periodontal ligament stem cells in periodontitis","volume":"29","author":"Cao","year":"2023","journal-title":"Oral Dis"},{"key":"10.1016\/j.identj.2025.100850_bib0035","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s13148-020-00982-7","article-title":"Epigenetic regulation of inflammation in periodontitis: cellular mechanisms and therapeutic potential","volume":"12","author":"Jurdzi\u0144ski","year":"2020","journal-title":"Clin Epigenetics"},{"key":"10.1016\/j.identj.2025.100850_bib0036","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/j.1432-0436.2007.00232.x","article-title":"Complementary roles for histone deacetylases 1, 2, and 3 in differentiation of pluripotent stem cells","volume":"76","author":"Humphrey","year":"2008","journal-title":"Differentiation"},{"key":"10.1016\/j.identj.2025.100850_bib0037","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1093\/emboj\/cdg315","article-title":"The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2","volume":"22","author":"Kr\u00e4mer","year":"2003","journal-title":"EMBO J"},{"key":"10.1016\/j.identj.2025.100850_bib0038","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1038\/s41380-020-00958-2","article-title":"Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2","volume":"26","author":"Logan","year":"2021","journal-title":"Mol Psychiatr"},{"key":"10.1016\/j.identj.2025.100850_bib0039","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/mt.2014.247","article-title":"HDAC Inhibitors Target HDAC5, Upregulate MicroRNA-125a-5p, and Induce Apoptosis in Breast Cancer Cells","volume":"23","author":"Hsieh","year":"2015","journal-title":"Mol. Ther"}],"container-title":["International Dental Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002065392500139X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002065392500139X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T15:09:20Z","timestamp":1762182560000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002065392500139X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["S002065392500139X"],"URL":"https:\/\/doi.org\/10.1016\/j.identj.2025.100850","relation":{},"ISSN":["0020-6539"],"issn-type":[{"value":"0020-6539","type":"print"}],"subject":[],"published":{"date-parts":[[2025,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"VPA Enhances Pulp Regeneration by Regulating LPS-Induced Human Dental Pulp Stem Cells Odontogenic Differentiation","name":"articletitle","label":"Article Title"},{"value":"International Dental Journal","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.identj.2025.100850","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc. on behalf of FDI World Dental Federation.","name":"copyright","label":"Copyright"}],"article-number":"100850"}}