title: Hypoxia mimetic deferoxamine influences the expression of histone acetylation- and DNA methylation-associated genes in osteoblasts.
abstract: OBJECTIVE
  Sufficient oxygen supply to bone tissue is essential for normal bone development and efficient bone repair. Hypoxia and hypoxia-inducible factor 1α (HIF1α) signaling pathway have been shown to exhibit profound effects on proliferation, differentiation as well as gene and protein expression in osteoblasts, osteoclasts and mesenchymal stem cells; however, as epigenetic mechanisms also perform an important regulatory role in these cells, our aim was to elucidate whether hypoxia mimetic deferoxamine could influence epigenetic mechanisms in bone cells by modulating the gene expression levels of chromatin-modifying enzymes.
  
  
  METHODS
  Osteoblast cell line HOS was exposed to deferoxamine, a widely used hypoxia mimetic, and expression profile of 40 genes associated with histone acetylation, deacetylation and DNA methylation was determined using quantitative real time polymerase chain reaction (qPCR) array followed by individual qPCR analyses. In addition, genes associated with hypoxia response, RANK/RANKL/OPG system, WNT/β-catenin signaling pathway and oxidative stress were also analyzed.
  
  
  RESULTS
  We observed induced expression of histone deacetylase 9 (HDAC9) and suppressed expression of K(lysine) acetyltransferase 5 (KAT5) and DNA methyltransferase 3A (DNMT3A) demonstrating for the first time that expression of genes encoding chromatin-modifying enzymes could be influenced by hypoxia mimetic in HOS cells.
  
  
  CONCLUSIONS
  Based on our results we can conclude that hypoxia mimetic deferoxamine influences expression of histone acetylation- and DNA methylation-associated genes in osteoblasts and that further studies of hypoxia-induced epigenetic changes in bone cells should be undertaken.
authors: Department of Clinical Biochemistry, Faculty of Pharmacy, University of Ljubljana , Ljubljana , Slovenia.
authors: Peter
authors: P
authors: Vrtačnik
authors: Janja
authors: J
authors: Marc
authors: Barbara
authors: B
authors: Ostanek
mesh_terms: D000107:Acetylation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D015687:Cell Hypoxia; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects*; D000090205:DNA Methyltransferase 3A; D003676:Deferoxamine / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D006657:Histones / Q000378:metabolism*; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: C000717967:DNMT3A protein, human; D006657:Histones; D000090205:DNA Methyltransferase 3A; D003676:Deferoxamine
keywords: Epigenetics; RANK/RANKL/OPG system; WNT/beta-catenin signaling pathway; oxidative stress; posttranslational histone modification