title: Nano-hydroxyapatite modulates osteoblast lineage commitment by stimulation of DNA methylation and regulation of gene expression.
abstract: Hydroxyapatite (HA) is the primary structural component of the skeleton and dentition. Under biological conditions, HA does not occur spontaneously and therefore must be actively synthesized by mineralizing cells such as osteoblasts. The mechanism(s) by which HA is actively synthesized by cells and deposited to create a mineralized matrix are not fully understood and the consequences of mineralization on cell function are even less well understood. HA can be chemically synthesized (HAp) and is therefore currently being investigated as a promising therapeutic biomaterial for use as a functional scaffold and implant coating for skeletal repair and dental applications. Here we investigated the biological effects of nano-HAp (10 × 100 nm) on the lineage commitment and differentiation of bone forming osteoblasts. Exposure of early stage differentiating osteoblasts resulted in dramatic and sustained changes in gene expression, both increased and decreased, whereas later stage osteoblasts were much less responsive. Analysis of the promoter region one of the most responsive genes, alkaline phosphatase, identified the stimulation of DNA methylation following cell exposure to nano-HAp. Collectively, the results reveal the novel epigenetic regulation of cell function by nano-HAp which has significant implication on lineage determination as well as identifying a novel potential therapeutic use of nanomaterials.
authors.affiliation: Department of Medicine, Division of Endocrinology Metabolism and Lipids, Emory University, Atlanta, GA 30322, United States.
authors.forename: Shin-Woo
authors.initials: SW
authors.lastname: Ha
authors.affiliation: Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors.forename: Hae Lin
authors.initials: HL
authors.lastname: Jang
authors.affiliation: Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors.forename: Ki Tae
authors.initials: KT
authors.lastname: Nam
authors.affiliation: The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033, United States; Department of Medicine, Division of Endocrinology Metabolism and Lipids, Emory University, Atlanta, GA 30322, United States; The Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, United States. Electronic address: george.beck@emory.edu.
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects*; D017886:Durapatite / Q000737:chemistry / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D017886:Durapatite; D000469:Alkaline Phosphatase
keywords: Alkaline phosphatase; Gene expression; Hydroxyapatite; Nanoparticle; Osteoblast; Osteogenesis