title: Effects of imatinib and nilotinib on the whole transcriptome of cultured murine osteoblasts.
abstract: Numerous clinical observations have confirmed that breakpoint cluster region-abelson fusion oncoprotein tyrosine kinase inhibitors used in leukemia treatment alter bone physiology in a complex manner. The aim of the present study was to analyze the whole transcriptome of cultured murine osteoblasts and determine the changes following treatment with imatinib and nilotinib using Sequencing by Oligonucleotide Ligation and Detection next generation RNA sequencing. This study also aimed to identify candidate signaling pathways and network regulators by multivariate Ingenuity Pathway Analysis. Based on the right-tailed Fisher's exact test, significantly altered pathways including upstream regulators were defined for each drug. The correlation between these pathways and bone metabolism was also examined. The preliminary results suggest the two drugs have different mechanisms of action on osteoblasts, and imatinib was shown to have a greater effect on gene expression. Data also indicated the potential role of a number of genes and signaling cascades that may contribute to identifying novel targets for the treatment of metabolic bone diseases.
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Gyöngyi
authors.initials: G
authors.lastname: Kirschner
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Balla
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Horváth
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kövesdi
authors.affiliation: Second Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Lakatos
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Takács
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Nagy
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Bálint
authors.initials: B
authors.lastname: Tóbiás
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Kristóf
authors.initials: K
authors.lastname: Árvai
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: János Pál
authors.initials: JP
authors.lastname: Kósa
authors.affiliation: First Department of Internal Medicine, Semmelweis University, 1083 Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D000068877:Imatinib Mesylate / Q000494:pharmacology*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib