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Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-кB signaling pathway

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Abstract

Naringin exhibits antiinflammatory activity and is shown to induce bone formation. Yet the impact of naringin on inflammation-affected bone marrow-derived mesenchymal stem cell (BM-MSC), a promising tool for the regenerative treatment of bone injury, remained to be investigated. We first cultured and characterized the BM-MSCs in vitro and observe the effects of treatments of TNF-α, naringin, or the combination of both on osteogenic differentiation. TNF-α administered at the concentration of 20 ng/ml results in significant reductions in MSC’s cell survival, alkaline phosphatase activity and expressions of two osteogenic genes, Runx2 and Osx. Simultaneous treatment of both TNF-α and naringin is able to rescue such reductions. Further mechanistic studies indicate that TNF-α treatment activates the NF-кB signaling pathway, evidenced by elevated p-IкBα level as well as the increased nuclear fraction of NF-кB subunit, p65. Finally, treatment with both TNF-α and naringin decreases expressions of p-IкBα and nuclear p65, and thus represses NF-кB pathway activated by sole TNF-α treatment. Our findings provide a molecular basis by which naringin restores the TNF-α-induced damage in MSCs and provide novel insights into the application of naringin in the MSC-based treatments for inflammation-induced bone injury.

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Acknowledgments

This work was supported by Shanghai municipal commission of health and family planning.

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The authors declare that they have no conflict of interest.

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All applicable international, national and/or institutional guidelines for the care and use of animals were followed.

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    Authors and Affiliations

    1. Department of Orthopaedics, Hua Dong Hospital Affiliated to Fudan University, Shanghai, 200040, China

      Xvhai Cao, Weilong Lin, Chengwei Liang, Dong Zhang, Fengjian Yang, Yan Zhang, Xuelin Zhang, Jianyong Feng & Cong Chen

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    Correspondence to Cong Chen.

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    Xvhai Cao, Weilong Lin and Chengwei Liang have contributed equally to this work.

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    Cao, X., Lin, W., Liang, C. et al. Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-кB signaling pathway. Immunol Res 62, 357–367 (2015). https://doi.org/10.1007/s12026-015-8665-x

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