Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of Runx2, OPG, and regucalcin mRNA expressions.
The effect of zinc sulfate on the mRNA expressions in Runx2, osteocalcin, alpha1(I) collagen, insulin-like growth factor-I (IGF-I), transforming growth factor-beta1 (TGF-beta1), osteoprotegerin (OPG), regucalcin, zinc transporter 1 (ZIP1), or glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) in osteoblastic MC3T3-E1 cells in vitro was investigated. Cells with subconfluency were cultured for 48 h in a medium containing either vehicle or zinc sulfate (10(-6)-10(-4) M) without fetal bovine serum. Culture with zinc sulfate (10(-5) M) caused a significant increase in Runx2, OPG, or regucalcin mRNA expressions in the cells, while it did not have a significant effect on osteocalcin, alpha1(I) collagen, IGF-I, TGF-beta1, ZIP1, or G3PDH mRNA expressions. The effect of zinc sulfate (10(-4) M) in increasing Runx2 mRNA expression was seen at 24-72 h after culture. A significant increase in OPG mRNA expression was observed at 24 or 48 h after culture. Regucalcin mRNA expression was significantly increased at 48 or 72 h after culture with zinc sulfate (10(-4) M). The stimulatory effects of zinc sulfate on Runx2, OPG, or regucalcin mRNAs were significantly prevented in the presence of cycloheximide (10(-7) M), an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (10(-6) M), an inhibitor of transcription activity. Culture with beta-alanyl-L-histidinato zinc (10(-5) M) caused a significant increase in Runx2 or regucalcin mRNA expressions, while zinc acexamate (10(-5) M) did not have a significant effect on Runx2, OPG, ZIP1, or regucalcin mRNA expressions. This study demonstrates that zinc sulfate has a role in the enhancement of Runx2, OPG, or regucalcin mRNA expression in osteoblastic cells in vitro, suggesting its role in the regulation of gene expression in the cells.
Yamaguchi
Masayoshi
M
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. yamamasa1155@yahoo.co.jp
Goto
Maya
M
Uchiyama
Satoshi
S
Nakagawa
Taeko
T
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002460:Cell Line; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin / Q000235:genetics*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D047908:Intracellular Signaling Peptides and Proteins; D053244:Osteoprotegerin; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; C513324:Rgn protein, mouse; C493716:Runx2 protein, mouse; C506031:Tnfrsf11b protein, mouse; D017967:Zinc Compounds; D004004:Dichlororibofuranosylbenzimidazole; D003513:Cycloheximide; D015032:Zinc