title: Inhibition of Histone Deacetylases Enhances the Osteogenic Differentiation of Human Periodontal Ligament Cells.
abstract: One of the characteristics of periodontal ligament (PDL) cells is their plasticity. Yet, the underlying mechanisms responsible for this phenomenon are unknown. One possible mechanism might be related to epigenetics, since histone deacetylases (HDACs) have been shown to play a role in osteoblast differentiation. This study was aimed to investigate the role of HDACs in osteogenic differentiation of human PDL (hPDL) cells. HDAC inhibitor trichostatin A (TSA) had no effect on cell viability as was assessed by MTT assay. Osteogenic and adipogenic differentiation was analyzed by gene expression, ALP activity and mineral deposition. Western blotting was used to investigate the effect of TSA on histone acetylation and protein expression. In the presence of the HDAC inhibitor osteogenic differentiation was induced; osteoblast-related gene expression was increased significantly. ALP activity and mineral nodule formation were also enhanced. Inhibition of HDACs did not induce differentiation into the adipocyte lineage. hPDL highly expressed HDACs of both class I (HDAC 1, 2, 3) and class II (HDAC 4, 6). During osteogenic differentiation HDAC 3 expression gradually decreased. This was apparent in the absence and presence of the inhibitor. The level of acetylated Histone H3 was increased during osteogenic differentiation. Inhibition of HDAC activity induced hyperacetylation of Histone H3, therefore, demonstrating Histone H3 as a candidate target molecule for HDAC inhibition. In conclusion, hPDL cells express a distinguished series of HDACs and these enzymes appear to be involved in osteogenic differentiation. This finding suggests a potential application of TSA for bone regeneration therapy by hPDL cells.
authors.affiliation: Mineralized Tissue Research Unit, Faculty of Dentistry Chulalongkorn University, Bangkok, Thailand.|DRU in Oral Microbiology, Department of Microbiology, Faculty of Dentistry Chulalongkorn University, Bangkok, Thailand.
authors.forename: Nam Cong-Nhat
authors.initials: NC
authors.lastname: Huynh
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Research Institute MOVE, Gustav Mahlerlaan 3004, 1081 LA Amsterdam, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
authors.affiliation: Mineralized Tissue Research Unit, Faculty of Dentistry Chulalongkorn University, Bangkok, Thailand.|Department of anatomy, Faculty of Dentistry Chulalongkorn University, Bangkok, Thailand.
authors.forename: Prasit
authors.initials: P
authors.lastname: Pavasant
authors.affiliation: DRU in Oral Microbiology, Department of Microbiology, Faculty of Dentistry Chulalongkorn University, Bangkok, Thailand.
authors.forename: Ruchanee Salingcarnboriboon
authors.initials: RS
authors.lastname: Ampornaramveth
mesh_terms: D000107:Acetylation; D050156:Adipogenesis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D000066670:Cell Plasticity / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A
keywords: HDAC INHIBITOR; HISTONE DEACETYLASE; OSTEOGENIC DIFFERENTIATION; PERIODONTAL LIGAMENT CELL; TRICHOSTATIN A