{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:06:17Z","timestamp":1789398377165,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, University and Research (MIUR), Italy","award":["DOT1353500"],"award-info":[{"award-number":["DOT1353500"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Bone healing is a major clinical issue, especially in bone defects of critical dimensions. Some studies have reported in vivo positive effects on bone healing by some bioactive compounds, such as the phenolic derivatives found in vegetables and plants, such as resveratrol, curcumin, and apigenin. The aim of this work was (1) to analyze in vitro in human dental pulp stem cells the effects of these three natural compounds on the gene expression of related genes downstream to RUNX2 and SMAD5, key factor transcriptions associated with osteoblast differentiation, in order to better understand the positive effects that can occur in vivo in bone healing, and (2) to evaluate in vivo the effects on bone healing of critical-size defects in the calvaria in rats of these three nutraceuticals tested in parallel and for the first time administered by the gastric route. Upregulation of the RUNX2, SMAD5, COLL1, COLL4, and COLL5 genes in the presence of apigenin, curcumin, and resveratrol was detected. In vivo, apigenin induced more consistent significant bone healing in critical-size defects in rat calvaria compared to the other study groups. The study findings encourage a possible therapeutic supplementation with nutraceuticals during the bone regeneration process.<\/jats:p>","DOI":"10.3390\/nu15051235","type":"journal-article","created":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T01:36:09Z","timestamp":1677634569000},"page":"1235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Effectiveness of Apigenin, Resveratrol, and Curcumin as Adjuvant Nutraceuticals for Calvarial Bone Defect Healing: An In Vitro and Histological Study on Rats"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2660-9231","authenticated-orcid":false,"given":"Felice","family":"Lorusso","sequence":"first","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1374-6146","authenticated-orcid":false,"given":"Antonio","family":"Scarano","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine & Dentistry, University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4557-9127","authenticated-orcid":false,"given":"Stefania","family":"Fulle","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5914-615X","authenticated-orcid":false,"given":"Luca","family":"Valbonetti","sequence":"additional","affiliation":[{"name":"Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Mancinelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9531-7788","authenticated-orcid":false,"given":"Ester Sara","family":"Di Filippo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Sciences, University \u201cG. d\u2019Annunzio\u201d of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5435\/00124635-199501000-00001","article-title":"Alternatives to Autogenous Bone Graft: Efficacy and Indications","volume":"3","author":"Gazdag","year":"1995","journal-title":"J. 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