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Lentivirus-mediated RNA interference of DC-STAMP expression inhibits the fusion and resorptive activity of human osteoclasts

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Abstract

Cell–cell fusion is a critical step in osteoclast development, because only after osteoclasts become multinucleated can they efficiently resorb bone. Although recent studies suggest that dendritic cell-specific transmembrane protein (DC-STAMP) may play a key role in the process of fusion of mouse osteoclasts, little information has been available on the role of DC-STAMP in human osteoclasts. In this study, we screened and identified an in vitro-transcribed short-hairpin RNA targeting human DC-STAMP from four candidates and generated a lentivirus vector. Subsequent experiments indicated that this lentiviral transgenic system could effectively transfer into target human osteoclasts, at more than 80 % gene transfer efficiency at multiplicity of infection of 15, and significantly and specifically inhibited DC-STAMP expression at both mRNA and protein levels. We also found that DC-STAMP inhibition by RNAi consequently suppressed fusion and bone resorption of human osteoclasts. In conclusion, these data indicated the lentivirus-mediated RNAi was capable of efficiently suppressing DC-STAMP expression in primary human osteoclasts and inhibiting osteoclastogenesis, demonstrating an essential role of DC-STAMP in the differentiation of human osteoclasts.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30871111 and No. 81172259) and the Natural Science Foundation of Fujian Province of China (No. 2011J05064).

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Authors and Affiliations

  1. Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Chating, 350005, Fuzhou, China

    Zhiyong Zeng & Junmin Chen

  2. Department of Medical Laboratory, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China

    Chenqing Zhang

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  1. Zhiyong Zeng
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  2. Chenqing Zhang
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  3. Junmin Chen
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Corresponding author

Correspondence to Junmin Chen.

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Zeng, Z., Zhang, C. & Chen, J. Lentivirus-mediated RNA interference of DC-STAMP expression inhibits the fusion and resorptive activity of human osteoclasts. J Bone Miner Metab 31, 409–416 (2013). https://doi.org/10.1007/s00774-013-0434-0

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  • DOI: https://doi.org/10.1007/s00774-013-0434-0

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