caa a22 4500 606234896 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2511-2 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2511-2 Edaravone protects osteoblastic cells from dexamethasone through inhibiting oxidative stress and mPTP opening [Elektronische Daten] [Wen-xiao Sun, Hai-ya Zheng, Jun Lan] 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. Springer Science+Business Media New York, 2015 Dexamethasone nationallicence Osteoblasts nationallicence Edaravone nationallicence Oxidative stress nationallicence Osteonecrosis nationallicence Sun Wen-xiao Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, Wuhan, China aut Zheng Hai-ya Department of Clinical Laboratory, The People's Hospital of Lishui, 323000, Lishui, Zhejiang, China aut Lan Jun Department of Orthopaedics, The People's Hospital of Lishui, 323000, Lishui, Zhejiang, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 51-58 0300-8177 409:1-2<51 2015 409 11010 https://doi.org/10.1007/s11010-015-2511-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2511-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sun Wen-xiao Department of Orthopedic and Hand Surgery, Liyuan Hospital, Huazhong University of Science and Technology, Wuhan, China aut NATIONALLICENCE 700 1- Zheng Hai-ya Department of Clinical Laboratory, The People's Hospital of Lishui, 323000, Lishui, Zhejiang, China aut NATIONALLICENCE 700 1- Lan Jun Department of Orthopaedics, The People's Hospital of Lishui, 323000, Lishui, Zhejiang, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 51-58 0300-8177 409:1-2<51 2015 409 11010