Bromopropane compounds inhibit osteogenesis by ERK-dependent Runx2 inhibition in C2C12 cells

• Published in: Archives of pharmacal research Vol. 37; no. 2; pp. 276 - 283
• Main Authors: Jeong, Hyung Min, Choi, You Hee, Jeong, Hye Gwang, Jeong, Tae Cheon, Lee, Kwang Youl
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2014; 대한약학회
• Subjects: alkaline phosphatase; Alkaline Phosphatase - metabolism; Animals; bone formation; Bone Morphogenetic Protein 2 - pharmacology; Cell Differentiation - drug effects; Core Binding Factor Alpha 1 Subunit - antagonists & inhibitors; Core Binding Factor Alpha 1 Subunit - genetics; Dose-Response Relationship, Drug; Extracellular Signal-Regulated MAP Kinases - metabolism; genetic markers; HEK293 Cells; Humans; Hydrocarbons, Brominated - pharmacology; immune system; Medicine; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - enzymology; Mesenchymal Stromal Cells - metabolism; Mice; mitogen-activated protein kinase; nervous system; Osteoblasts - drug effects; Osteogenesis - drug effects; Pharmacology/Toxicology; Pharmacy; Propane - analogs & derivatives; Propane - pharmacology; Research Article; solvents; Sp7 Transcription Factor; stem cells; transcription (genetics); transcription factors; Transcription Factors - genetics; Transcription, Genetic - drug effects; 약학; Bromopropane; JNK; Osteoblast differentiation; Runx2; ERK
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-013-0178-3

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.