{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T04:46:31Z","timestamp":1779165991685,"version":"3.51.4"},"reference-count":67,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T00:00:00Z","timestamp":1551744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PON 01_02834"],"award-info":[{"award-number":["PON 01_02834"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2010\/11 N. 201002M7T8X002"],"award-info":[{"award-number":["PRIN 2010\/11 N. 201002M7T8X002"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Epigenetic regulation has been considered an important mechanism for influencing stem cell differentiation. In particular, histone deacetylases (HDACs) have been shown to play a role in the osteoblast differentiation of mesenchymal stem cells (MSCs). In this study, the effect of the HDAC inhibitor, valproic acid (VPA), on bone formation in vivo by MSCs was determined. Surprisingly, VPA treatment, unlike other HDAC inhibitors, produced a well-organized lamellar bone tissue when MSCs\u2013collagen sponge constructs were implanted subcutaneously into nonobese diabetic\/severe combined immunodeficiency (NOD\/SCID) mice, although a decrease of osteocalcin (OC) expression was observed. Consequently, we decided to investigate the molecular mechanisms by which VPA exerts such effects on MSCs. We identified the glucocorticoid receptor (GR) as being responsible for that downregulation, and suggested a correlation between GR and HDAC2 inhibition after VPA treatment, as evidenced by HDAC2 knockdown. Furthermore, using co-immunoprecipitation analysis, we showed for the first time in the cytoplasm, binding between GR and HDAC2. Additionally, chromatin immunoprecipitation (ChIP) assays confirmed the role of GR in OC downregulation, showing recruitment of GR to the nGRE element in the OC promoter. In conclusion, our results highlight the existence of a cross-talk between GR and HDAC2, providing a mechanistic explanation for the influence of the HDAC inhibitor (namely VPA) on osteogenic differentiation in MSCs. Our findings open new directions in targeted therapies, and offer new insights into the regulation of MSC fate determination.<\/jats:p>","DOI":"10.3390\/cells8030217","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T11:19:50Z","timestamp":1551784790000},"page":"217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Cytoplasmic Interactions between the Glucocorticoid Receptor and HDAC2 Regulate Osteocalcin Expression in VPA-Treated MSCs"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8782-3821","authenticated-orcid":false,"given":"Marcella","family":"La Noce","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Mele","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Laino","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical-Surgical and Odontostomatological Specialties, University of Campania, \u201cLuigi Vanvitelli\u201d, 80121 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Iolascon","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties and Dentistry, University of Campania \u201cLuigi Vanvitelli\u201d, 80121 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gorizio","family":"Pieretti","sequence":"additional","affiliation":[{"name":"Multidisciplinary Department of Medical-Surgical and Odontostomatological Specialties, University of Campania, \u201cLuigi Vanvitelli\u201d, 80121 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-5306","authenticated-orcid":false,"given":"Gianpaolo","family":"Papaccio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1819-6083","authenticated-orcid":false,"given":"Vincenzo","family":"Desiderio","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Tirino","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-1888","authenticated-orcid":false,"given":"Francesca","family":"Paino","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-pathol-011110-130203","article-title":"Disorders of bone remodeling","volume":"6","author":"Feng","year":"2011","journal-title":"Annu. 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