title: Lentiviral-mediated RNAi targeting p38MAPK ameliorates high glucose-induced apoptosis in osteoblast MC3T3-E1 cell line.
abstract: The p38 mitogen activated protein kinase (p38MAPK) pathway is an important signaling cascade involved in cell growth, differentiation and apoptosis. High glucose activates p38MAPK pathway in different cells, including osteoblasts. In the present study, role of p38MAPK in high glucose induced osteoblast apoptosis and potential of RNA interference (RNAi) targeting p38MAPK as a therapy strategy have been reported. Lentiviral-mediated RNAi effectively reduced p38MAPK and p-p38MAPK expressions in osteoblastic cell line (MC3T3-E1) following high glucose (22 mM) induction. Inhibition of p38MAPK activity significantly suppressed high glucose induced apoptosis of MC3T3-E1 cell and was confirmed by flow cytometry and ultra-structural examination by transmission electronic microscope. Inhibition of p38MAPK also significantly attenuates caspase-3 and bax protein expressions, but increased significantly bcl-2 expression as determined by Western blot analysis. The results suggested that p38MAPK mediates high glucose induced osteoblast apoptosis, partly through modulating the expressions of caspase-3, bax and bcl-2. Inhibition of p38MAPK with lentiviral-mediated RNAi or its specific inhibitor provides a new strategy to treat high glucose induced osteoblast apoptosis.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Feng
authors.forename: Huacong
authors.initials: H
authors.lastname: Deng
authors.forename: Jia
authors.initials: J
authors.lastname: Du
authors.forename: Danyan
authors.initials: D
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D016086:Lentivirus / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose