Suberoylanilide Hydroxamic Acid Enhances Odontoblast Differentiation

• Published in: Journal of dental research Vol. 91; no. 5; pp. 506 - 512
• Main Authors: Kwon, A., Park, H.-J., Baek, K., Lee, H.-L., Park, J.-C., Woo, K.M., Ryoo, H.-M., Baek, J.-H.
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.05.2012; SAGE PUBLICATIONS, INC
• Subjects: Animals; Binding sites; Bone growth; Cancer; Cell differentiation; Cell Differentiation - drug effects; Cell Line; Cytotoxicity; Dentin; Dentistry; Dspp protein; Extracellular Matrix Proteins - biosynthesis; Extracellular Matrix Proteins - genetics; Gene expression; Gene Knockdown Techniques; Histone deacetylase; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - metabolism; Hydroxamic acid; Hydroxamic Acids - pharmacology; Mice; Mineralization; Mutation; NFI Transcription Factors - genetics; NFI Transcription Factors - metabolism; Nuclear factor I; Odontoblasts; Odontoblasts - drug effects; Osteoblastogenesis; Osteogenesis; Phosphoproteins - biosynthesis; Phosphoproteins - genetics; Promoter Regions, Genetic; Proteins; RNA, Small Interfering - physiology; Sialoglycoproteins - biosynthesis; Sialoglycoproteins - genetics; siRNA; Stains & staining; Stem cells; Transcription; Up-Regulation; United States > US; dentin sialophosphoprotein; SAHA; promoter; transcription; MDPC23 cells; Nfic
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/0022034512443367

Previous studies have shown that histone deacetylase (HDAC) inhibitors stimulate osteoblast differentiation in vitro and bone formation in vivo. However, the effects of HDAC inhibitors on odontoblasts have not been elucidated. Therefore, in this study, we examined the effect of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on odontoblast differentiation using an MDPC23 odontoblast-like cell line. SAHA significantly enhanced matrix mineralization and the expression levels of odontoblast marker genes. SAHA increased the expression levels of nuclear factor I/C (Nfic) and dentin sialophosphoprotein (Dspp). Nfic bound directly to the Dspp promoter and stimulated Dspp transcription. SAHA increased both basal and Nfic-induced Dspp promoter activity. SAHA-induced Dspp promoter activity disappeared when mutations were introduced within the Nfic binding element of the Dspp promoter. Nfic knockdown by siRNA blocked SAHA stimulation of Dspp expression. These results indicate that SAHA enhances odontoblast differentiation and that SAHA increases Dspp expression, at least in part, by increasing the expression level of Nfic.