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Fullerol antagonizes dexamethasone-induced oxidative stress and adipogenesis while enhancing osteogenesis in a cloned bone marrow mesenchymal stem cell.

Research paper by Hongjian H Liu, Xinlin X Yang, Yi Y Zhang, Abhijit A Dighe, Xudong X Li, Quanjun Q Cui

Indexed on: 10 May '12Published on: 10 May '12Published in: Journal of Orthopaedic Research



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.