title: Nicotinic modulation of gene expression in osteoblast cells, MG-63.
abstract: Exposure to nicotine causes a broad range of biological and molecular effects on osteoblasts which are known to play a crucial role in bone metabolism and fracture healing. Most effects of nicotine on the osteoblasts are long-term adaptations at the genomic level. To identify the nicotine-regulated genes, the Agilent technologies whole human genome gene expression microarray was performed on RNA samples from osteoblast-like cells, MG-63, exposed to 100 μM nicotine. Repeat and cross-controlled microarray analyses revealed 842 genes whose expression was consistently altered at P<0.05 level following nicotine treatment. Gene ontology analysis suggested effects of nicotine on various biological and cellular processes which were associated with survival, proliferation, differentiation and apoptosis processes within the cell. Quantitative real-time reverse transcriptase PCR analysis confirmed altered expression in 7 out of 9 genes tested. The identified genes tested in the current study support our previous report that nicotine regulates the expression of genes that promote osteoblast proliferation and/or anti-apoptosis processes. Furthermore, using nicotinic acetylcholine receptor antagonists blocked the majority of the nicotine effects, indicating that these changes are dependent on nAChR activation. These results established a novel and consistent nicotinic activation of nAChR in osteoblast cells which has a broad role affecting cellular physiology through modulation of gene expression.
authors.affiliation: Department of Orthopaedic Surgery A, Rambam Health Care Campus, Haifa, Israel. d_rothem@rambam.health.gov.il
authors.forename: David E
authors.initials: DE
authors.lastname: Rothem
authors.forename: Lilah
authors.initials: L
authors.lastname: Rothem
authors.forename: Aviva
authors.initials: A
authors.lastname: Dahan
authors.forename: Rami
authors.initials: R
authors.lastname: Eliakim
authors.forename: Michael
authors.initials: M
authors.lastname: Soudry
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018733:Nicotinic Antagonists; D009538:Nicotine