title: Bromopropane compounds inhibit osteogenesis by ERK-dependent Runx2 inhibition in C2C12 cells.
abstract: Bromopropane (BP) is a halogenated alkan compound used in various industries as chemical intermediates, extraction solvents, and degreasing compounds. Halogenated alkan compounds can damage the nervous system, immune system, and hematopoietic and reproductive functions in animals and humans. However, the effect of BPs on bone formation has not yet been examined. This study examined the effects of BPs on osteoblast differentiation and analyzed the mechanisms involved in C2C12, mesenchymal stem cells. BPs dose dependently reduced the alkaline phosphatase activity, expression levels and promoter activity of bone marker genes. Additionally, 1,2-dibromopropane (1,2-DBP) significantly reduced the levels and transcriptional activity of Runx2 and Osterix, major bone transcription factors, in BMP2 induced C2C12 cells. Furthermore, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were significantly inhibited by 1,2-DBP. These results demonstrate that BPs inhibit osteoblast differentiation by suppressing Runx2 and Osterix through the ERK/JNK pathway.
authors.affiliation: College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Jeong
authors.forename: You Hee
authors.initials: YH
authors.lastname: Choi
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D011407:Propane / Q000031:analogs & derivatives / Q000494:pharmacology; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D006842:Hydrocarbons, Brominated; C493716:Runx2 protein, mouse; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors; D048049:Extracellular Signal-Regulated MAP Kinases; D000469:Alkaline Phosphatase; C050753:1,2-dibromopropane; D011407:Propane; C118559:1-bromopropane; C032699:1,3-dibromopropane