{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T23:06:26Z","timestamp":1765667186421,"version":"3.37.3"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,5,10]],"date-time":"2017-05-10T00:00:00Z","timestamp":1494374400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470733","81271125"],"award-info":[{"award-number":["81470733","81271125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2018,7]]},"abstract":"Abstract<\/jats:title>Aim<\/jats:title>To investigate the growth, migratory and adhesive effects of trichostatin A (TSA<\/jats:styled-content>) and valproic acid (VPA<\/jats:styled-content>), two histone deacetylase inhibitors (HDAC<\/jats:styled-content>is), on human dental pulp stem cells (hDPSC<\/jats:styled-content>s).<\/jats:p><\/jats:sec>Methodology<\/jats:title>To verify that TSA<\/jats:styled-content> or VPA<\/jats:styled-content> functions as an HDAC<\/jats:styled-content> inhibitor, the expressions of histones H3 and H4 were examined using Western blotting analysis. hDPSC<\/jats:styled-content> growth and metabolic activity was evaluated by MTT<\/jats:styled-content> viability analysis at different time\u2010points and by cell count experiments. The expression of cell cycle regulatory proteins and apoptosis\u2010associated proteins was examined by Western blot analysis. Migration effects were investigated using wound healing and transwell migration assays. An adhesion assay was also performed in the presence and absence of HDAC<\/jats:styled-content>is. The levels of chemokines and adhesion molecules relevant to repair in hDPSC<\/jats:styled-content>s were also assessed by qRT<\/jats:styled-content>\u2010PCR<\/jats:styled-content> and Western blot analysis. The data were analysed, where appropriate, using Student's t\u2010test or one\u2010way anova<\/jats:sc> followed by the Student\u2013Newman\u2013Keuls test using SPSS<\/jats:styled-content> software.<\/jats:p><\/jats:sec>Results<\/jats:title>Trichostatin A and VPA<\/jats:styled-content> enhanced acetylation of histones H3 and H4 (P<\/jats:italic>\u00a0<\u00a00.05). Significant increases (P<\/jats:italic>\u00a0<\u00a00.05) in MTT<\/jats:styled-content> levels in hDPSC<\/jats:styled-content>s were\u00a0observed after treatment with TSA<\/jats:styled-content> (2 and 20\u00a0nmol\u00a0L\u22121<\/jats:sup>) or VPA<\/jats:styled-content> (1 and 10\u00a0mmol\u00a0L\u22121<\/jats:sup>). Cell numbers were not significantly affected at the concentration of TSA<\/jats:styled-content> (0.2\u201310\u00a0nmol\u00a0L\u22121<\/jats:sup>) or VPA<\/jats:styled-content> (0.01\u2013100\u00a0mmol\u00a0L\u22121<\/jats:sup>) applied compared with the control at 3, 5 or 7\u00a0days (P\u00a0<\/jats:italic>>\u00a00.05). At the same time, the expression of Cdx2 and cyclin A was upregulated by 2\u00a0nmol\u00a0L\u22121<\/jats:sup> TSA<\/jats:styled-content> and 1\u00a0mmol\u00a0L\u22121<\/jats:sup> VPA<\/jats:styled-content> (P<\/jats:italic>\u00a0<\u00a00.05). Higher TSA<\/jats:styled-content> or VPA<\/jats:styled-content> concentrations induced apoptosis in hDPSC<\/jats:styled-content>s in the cell count and apoptosis experiments (P<\/jats:italic>\u00a0<\u00a00.05). Moreover, TSA<\/jats:styled-content> and VPA<\/jats:styled-content> significantly depressed the expression of Cdx2 and cyclin A (P<\/jats:italic>\u00a0<\u00a00.05), whilst it significantly improved the level of p21 (P<\/jats:italic>\u00a0<\u00a00.05). TSA<\/jats:styled-content> and VPA<\/jats:styled-content> promoted migration and adhesion of hDPSC<\/jats:styled-content>s (P<\/jats:italic>\u00a0<\u00a00.05). The levels of chemokines and adhesion molecules were significantly upregulated after exposure of hDPSC<\/jats:styled-content>s to 20\u00a0nmol\u00a0L\u22121<\/jats:sup> TSA<\/jats:styled-content> or 1\u00a0mmol\u00a0L\u22121<\/jats:sup> VPA<\/jats:styled-content> (P<\/jats:italic>\u00a0<\u00a00.05).<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Histone deacetylase inhibitors at specific concentrations promoted proliferation, migration and adhesion of hDPSC<\/jats:styled-content>s, which may contribute to novel regenerative therapies for pulpal disease treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.12779","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T17:05:49Z","timestamp":1491411949000},"page":"767-778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Effects of histone deacetylase inhibitors on regenerative cell responses in human dental pulp 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