title: Involvement of AP-1 in p38MAPK signaling pathway in osteoblast apoptosis induced by high glucose.
abstract: We investigated the effect of p38MAPK/AP-1 (activator protein-1) signaling on the apoptosis of osteoblasts induced by high glucose. A lentivirus vector of small hairpin RNA (shRNA) targeting p38MAPK was constructed in vitro. Osteoblasts MC3T3-E1 cultured in vitro were treated with vehicle, high glucose, p38MAPK-shRNA transfection, p38MAPK inhibitor, and unrelated shRNA transfection. Apoptosis, protein levels of p38MAPK, and activities of AP-1 in MC3T3-E1 osteoblasts were measured using TUNEL and flow cytometry, Western blot analysis, and an electrophoretic mobility shift assay. Compared with the vehicle group, high glucose induced apoptosis of MC3T3-E1 osteoblasts and activated p38MAPK and AP-1. p38MAPK-shRNA transfection blocked the effect of high glucose stimulation, and the p38MAPK inhibitor showed similar effects as those observed in p38MAPK transfection. Unrelated shRNA had no effect on these changes in MC3T3-E1 osteoblasts induced by high glucose. Therefore, our results suggest that p38MAPK-shRNA reduce apoptosis of MC3T3-E1 osteoblasts induced by high glucose by inhibiting the p38MAPK-AP-1 signaling pathway.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China fengzhengping_f@yeah.net.
authors.forename: Z P
authors.initials: ZP
authors.lastname: Feng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: H C
authors.initials: HC
authors.lastname: Deng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: R
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: D Y
authors.initials: DY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; C093642:SB 203580