title: Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening.
abstract: Existing evidences have emphasized an important role of oxidative stress in dexamethasone (Dex)-induced osteoblastic cell damages. Here, we investigated the possible anti-Dex activity of edaravone in osteoblastic cells, and studied the underlying mechanisms. We showed that edaravone dose-dependently attenuated Dex-induced death and apoptosis of established human or murine osteoblastic cells. Further, Dex-mediated damages to primary murine osteoblasts were also alleviated by edaravone. In osteoblastic cells/osteoblasts, Dex induced significant oxidative stresses, tested by increased levels of reactive oxygen species and lipid peroxidation, which were remarkably inhibited by edaravone. Meanwhile, edaravone repressed Dex-induced mitochondrial permeability transition pore (mPTP) opening, or mitochondrial membrane potential reduction, in osteoblastic cells/osteoblasts. Significantly, edaravone-induced osteoblast-protective activity against Dex was alleviated with mPTP inhibition through cyclosporin A or cyclophilin-D siRNA. Together, we demonstrate that edaravone protects osteoblasts from Dex-induced damages probably through inhibiting oxidative stresses and following mPTP opening.
authors.affiliation: Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wen-xiao
authors.initials: WX
authors.lastname: Sun
authors.affiliation: Department of Clinical Laboratory, The People's Hospital of Lishui, Lishui, 323000, Zhejiang, China.
authors.forename: Hai-ya
authors.initials: HY
authors.lastname: Zheng
authors.affiliation: Department of Orthopaedics, The People's Hospital of Lishui, Lishui, 323000, Zhejiang, China. clinlablanjunls@163.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Lan
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D021983:Cyclophilins / Q000235:genetics; D016572:Cyclosporine; D003907:Dexamethasone / Q000494:pharmacology*; D000077553:Edaravone; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D010020:Osteonecrosis / Q000139:chemically induced / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D034622:RNA Interference; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D000097322:Peptidyl-Prolyl Isomerase D
chemical_list: D000983:Antipyrine; D053148:Caspase 3; D021983:Cyclophilins; D016572:Cyclosporine; D003907:Dexamethasone; D000077553:Edaravone; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C114456:PPID protein, human; D000097322:Peptidyl-Prolyl Isomerase D
keywords: Dexamethasone; Edaravone; Osteoblasts; Osteonecrosis; Oxidative stress