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Plumbagin protects against glucocorticoid-induced osteoporosis through Nrf-2 pathway

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Cell Stress and Chaperones Aims and scope

Abstract

Long-term and high-dose glucocorticoids (GCs) supplementation has been linked to osteoporosis. In this study, we studied the protective role of plumbagin against GC-induced cell damage in MC3T3-E1 cells. The effect of dexamethasone (DEX) and plumbagin on cell viability was determined. DEX showed as IC-50 value of 95 μM. Further, 10 μM plumbagin treatment effectively ameliorated DEX-induced cell death by increasing the cell viability to 92 %. A further effect of plumbagin on DEX-induced oxidative stress was determined through reactive oxygen species (ROS) level, lipid peroxide content, and antioxidant status. Nrf-2 nuclear localization was analyzed through immunofluorescence. Protein expression of redox regulator Nrf-2 and their target genes HO-1 and NQO1 and osteogenic markers (OCN, OPN Runx-2) were determined by Western blot. Apoptotic effect was analyzed by mitochondrial membrane potential and caspase activities (3, 8, and 9). The results showed that DEX treatment showed a significant increase in oxidative stress through increased ROS levels and downregulation of cytoprotective antioxidant proteins and antioxidant enzyme activities. Further DEX treatment downregulated the osteogenic markers and upregulated apoptosis through decreased mitochondrial membrane potential and upregulation of caspase activities. Plumbagin treatment significantly reversed the levels of oxidative stress and apoptotic markers and protected against DEX-induced cell damage. Further, plumbagin treatment significantly improved the expression of osteogenic markers compared to DEX treatment. In conclusion, the present study shows that plumbagin offers significant protective role against DEX-induced cellular damage via regulating oxidative stress, apoptosis, and osteogenic markers.

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    Authors and Affiliations

    1. Department of Orthopedics, Qilu Hospital of Shandong University, No. 107 Wenhuaxi Road, Jinan, Shandong, 250012, China

      Shuai Zhang & Ting-Bin Yan

    2. Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China

      Dong Li

    3. Department of Pathology, The Second Hospital of Shandong University, Jinan, Shandong, 250033, China

      Jing-Yan Yang

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    1. Shuai Zhang
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    2. Dong Li
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    3. Jing-Yan Yang
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    Correspondence to Ting-Bin Yan.

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    Shuai Zhang and Dong Li contributed equally to this work.

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    Zhang, S., Li, D., Yang, JY. et al. Plumbagin protects against glucocorticoid-induced osteoporosis through Nrf-2 pathway. Cell Stress and Chaperones 20, 621–629 (2015). https://doi.org/10.1007/s12192-015-0585-0

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