title: Fullerol antagonizes dexamethasone-induced oxidative stress and adipogenesis while enhancing osteogenesis in a cloned bone marrow mesenchymal stem cell.
abstract: Increased oxidative stress is currently considered as a crucial cause of corticosteroid-induced osteonecrosis. The aim of this study was to evaluate the effect of fullerol, a powerful antioxidant, on adipogenic and osteogenic differentiation of a mouse bone marrow derived multipotent cell line, D1. Upon treatment with dexamethasone, D1 cells containing lipid vesicles were distinguishable from the surrounding cells by Oil Red O staining at day 21. Simultaneous treatment of dexamethasone with antioxidant glutathione or fullerol decreased the number of cells containing lipid vesicles. Treatment with dexamethasone for 7 days resulted in a significant increase in adipogenic markers peroxisome proliferator-activated receptor gamma and adipocyte protein 2 gene expression and decrease in expression of osteogenic markers runt-related transcription factor 2 and osteocalcin and antioxidative enzymes superoxide dismutase and catalase as revealed by quantitative real-time PCR. While glutathione and fullerol both were able to antagonize the effects of dexamethasone, fullerol had a greater effect than glutathione. Staining with a fluorescent dye CM-H(2) DCFDA as indicator of cellular reactive oxygen species revealed that the percentage of positively stained cells increased after dexamethasone treatment, and addition of fullerol attenuated this activity. These results indicated that fullerol inhibited adipogenesis and simultaneously enhanced osteogenesis by marrow mesenchymal stem cells possibly through elimination of cellular reactive oxygen species. The results indicated that fullerol can potentially be used for prevention and treatment of corticosteroid-induced osteonecrosis.
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Virginia School of Medicine, Hospital Drive, Charlottesville, Virginia, USA.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Liu
authors.forename: Xinlin
authors.initials: X
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Abhijit
authors.initials: A
authors.lastname: Dighe
authors.forename: Xudong
authors.initials: X
authors.lastname: Li
authors.forename: Quanjun
authors.initials: Q
authors.lastname: Cui
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D037741:Fullerenes / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010012:Osteogenesis / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: D037741:Fullerenes; D005938:Glucocorticoids; D017382:Reactive Oxygen Species; C496652:fullerol C60(OH)22; C408042:fullerol C60(OH)24; D003907:Dexamethasone; D002374:Catalase; D013482:Superoxide Dismutase