{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:02:59Z","timestamp":1793451779484,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"EU PON","award":["01_02834"],"award-info":[{"award-number":["01_02834"]}]},{"name":"MIUR PRIN"},{"name":"project of relevant interest","award":["20102M7T8X_002"],"award-info":[{"award-number":["20102M7T8X_002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Adult mesenchymal stem cells, such as dental pulp stem cells, are of great interest for cell-based tissue engineering strategies because they can differentiate into a variety of tissue-specific cells, above all, into osteoblasts. In recent years, epigenetic studies on stem cells have indicated that specific histone alterations and modifying enzymes play essential roles in cell differentiation. However, although several studies have reported that valproic acid (VPA)\u2014a selective inhibitor of histone deacetylases (HDAC)\u2014enhances osteoblast differentiation, data on osteocalcin expression\u2014a late-stage marker of differentiation\u2014are limited. We therefore decided to study the effect of VPA on dental pulp stem cell differentiation. A low concentration of VPA did not reduce cell viability, proliferation, or cell cycle profile. However, it was sufficient to significantly enhance matrix mineralization by increasing osteopontin and bone sialoprotein expression. In contrast, osteocalcin levels were decreased, an effect induced at the transcriptional level, and were strongly correlated with inhibition of HDAC2. In fact, HDAC2 silencing with shRNA produced a similar effect to that of VPA treatment on the expression of osteoblast-related markers. We conclude that VPA does not induce terminal differentiation of osteoblasts, but stimulates the generation of less mature cells. Moreover, specific suppression of an individual HDAC by RNA interference could enhance only a single aspect of osteoblast differentiation, and thus produce selective effects. Stem Cells \u00a02014;32:279\u2013289<\/jats:p>","DOI":"10.1002\/stem.1544","type":"journal-article","created":{"date-parts":[[2013,10,8]],"date-time":"2013-10-08T14:27:14Z","timestamp":1381242434000},"page":"279-289","source":"Crossref","is-referenced-by-count":131,"title":["Histone Deacetylase Inhibition with Valproic Acid Downregulates Osteocalcin Gene Expression in Human Dental Pulp Stem Cells and Osteoblasts: Evidence for HDAC2 Involvement"],"prefix":"10.1093","volume":"32","author":[{"given":"Francesca","family":"Paino","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Sperimentale Sezione di Istologia (TERM Lab.), via L. Armanni, 5, Secondo Ateneo di Napoli, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Noce","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale Sezione di Istologia (TERM Lab.), via L. 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