title: Zinc upregulates the expression of osteoprotegerin in mouse osteoblasts MC3T3-E1 through PKC/MAPK pathways.
abstract: Zinc is an essential element for bone formation; however, its role in osteoblast has not been well understood. In the present study, we hypothesized that zinc could increase osteogenetic function by stimulating osteoblast proliferation and osteoprotegerin (OPG) activity. To test this hypothesis, osteoblastic MC3T3-E1 cells were cultured and treated with various concentrations of zinc (0, 10, 30, 50, 70, 110, 130, and 150 μM) for 24 and 48 h. 3-[4,5-dimethylthiazol-2-y]-2,5-diphenyltetrazolium bromide assay showed that cell proliferation was significantly stimulated with 50 μM zinc treatment. Furthermore, under the same treatment condition, OPG expression was significantly increased as evidenced by the results of RT-PCR and ELISA. However, the zinc-induced OPG expression was significantly attenuated when MC3T3-E1 cells were co-treated with either protein kinase C (PKC) inhibitor, GF109203X, or the Inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1), PD98059. Moreover, OPG expression was further increased when MC3T3-E1 cells were treated with PMA (the activator of protein of kinase C) in the presence of zinc. These results suggested that zinc would increase osteogenic function by stimulating PKC and MAPK signaling pathways.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang, Liaoning, People's Republic of China. dl7711@163.com
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.forename: Maowei
authors.initials: M
authors.lastname: Yang
authors.forename: Baolei
authors.initials: B
authors.lastname: Guo
authors.forename: Junjun
authors.initials: J
authors.lastname: Cao
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: XiaoDong
authors.initials: X
authors.lastname: Guo
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D019287:Zinc Sulfate / Q000494:pharmacology*
chemical_list: D053244:Osteoprotegerin; D012333:RNA, Messenger; D019287:Zinc Sulfate; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases