{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T13:23:44Z","timestamp":1781616224532,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017M3A9B3063636"],"award-info":[{"award-number":["2017M3A9B3063636"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1I1A1A01046931"],"award-info":[{"award-number":["2021R1I1A1A01046931"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C1086767"],"award-info":[{"award-number":["2019R1A2C1086767"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Our previous study found that the level of CCN1 increases as osteogenic differentiation progresses in tonsil-derived mesenchymal stem cells (TMSCs). This study investigated how CCN1 is regulated through HDAC inhibition in TMSCs and their relationship with osteogenesis. Valproic acid (VPA) (1\u20135 mM), a well-known histone deacetylase (HDAC) inhibitor, strongly inhibited TMSC proliferation without altering MSC-specific surface markers, CD14, 34, 45, 73, 90 and 105. However, CD146 expression increased at 5 mM VPA. VPA increased osteogenic differentiation of TMSCs but decreased adipogenesis and chondrogenesis, as evidenced by the cell-specific staining of differentiation. The former was validated by the increased osteocalcin (OCN). The changes in CCN1 by VPA was biphasic; it increased until 48 h and decreased thereafter. Knockdown of CCN1 by using siRNA inhibited the osteogenic effect of VPA. VPA had no effect on CCN1 mRNA expression, but inhibition of protein synthesis by cycloheximide showed that VPA slowed down the CCN1 protein degradation. Moreover, overexpression of HDAC1 completely inhibited VPA-induced CCN1. Our results indicate that VPA inhibits the HDAC1, inducing CCN1 protein stability rather than gene expression, thereby promoting osteogenic differentiation of TMSCs. These findings present the noble implication of VPA as an inhibitor of HDAC1 to facilitate CCN1-induced osteogenic differentiation of MSCs.<\/jats:p>","DOI":"10.3390\/cells11030534","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T11:35:17Z","timestamp":1643974517000},"page":"534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Yeonsil","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, College of Medicine, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Korea"},{"name":"Global Business Development Division, Kangstem Biotech Co., Ltd., 512 Teheran-ro, Gangnam-gu, Seoul 06179, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9422-1079","authenticated-orcid":false,"given":"Se-Young","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, College of Medicine, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Korea"},{"name":"Graduate Program in System Health Science and Engineering, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ha Yeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea"},{"name":"Department of Pharmacology, College of Pharmacy, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangmee Ahn","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea"},{"name":"Department of Pharmacology, College of Pharmacy, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6060-6416","authenticated-orcid":false,"given":"Inho","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, College of Medicine, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Korea"},{"name":"Graduate Program in System Health Science and Engineering, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1002\/stem.3058","article-title":"Application of Tonsil-Derived Mesenchymal Stem Cells in Tissue Regeneration: Concise Review","volume":"37","author":"Oh","year":"2019","journal-title":"Stem Cells"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.biomaterials.2015.06.044","article-title":"Differentiated Tonsil-Derived Mesenchymal Stem Cells Embedded in Matrigel Restore Parathyroid Cell Functions in Rats with Parathyroidectomy","volume":"65","author":"Park","year":"2015","journal-title":"Biomaterials"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8616","DOI":"10.1038\/srep08616","article-title":"Tonsil-Derived Mesenchymal Stem Cells Ameliorate CCl4-Induced Liver Fibrosis in Mice via Autophagy Activation","volume":"5","author":"Park","year":"2015","journal-title":"Sci. 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