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RETRACTED ARTICLE: Bufalin Exerts Inhibitory Effects on IL-1β-Mediated Proliferation and Induces Apoptosis in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes

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This article was retracted on 18 February 2023

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Abstract

Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) proliferate abnormally and resist apoptosis. Bufalin inhibits cell proliferation and induces apoptosis in human cancer cells. In this study, we explored the effects of bufalin on interleukin-1beta (IL-1β)-induced proliferation and apoptosis of RAFLSs. The cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining, respectively. Bufalin dose-dependently inhibited IL-1β-induced RAFLS proliferation. Mechanistically, bufalin decreased the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB), both of which are involved in IL-1β-mediated RAFLS proliferation. Moreover, bufalin induced apoptosis and mitochondrial damage of RAFLSs, which was associated with Bcl-2 downregulation, Bax upregulation, mitochondrial cytochrome c release, and enhanced cleavages of caspase-3 and poly-(ADP-ribose) polymerase. Collectively, our results reveal that bufalin suppresses IL-1β-induced proliferation of RAFLSs through MAPK and NF-κB signaling pathways and induces RAFLS apoptosis via the mitochondria-dependent pathway.

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Acknowledgments

This work was supported by a grant (13ZR1442500) from the Natural Science Foundation of Shanghai.

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Authors and Affiliations

  1. Department of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Yue-wen Chang, Yong-fang Zhao, Yue-long Cao, Wei Gu, Jian Pang & Hong-sheng Zhan

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  1. Yue-wen Chang
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Correspondence to Yue-wen Chang or Yong-fang Zhao.

ELECTRONIC SUPPLEMENTARY MATERIAL

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Supplementary Fig. 1

DMOS does not affect IL-1β-induced RAFLS proliferation. Human RAFLSs were cultured with 1 ng/ml IL-1β in the presence or absence of DMSO (0.01 %, v/v) for 72 h. Cell viability was determined by MTT assay. The absorbance was measured at a 490-nm wavelength. Data are the mean ± SD of three independent experiments performed in triplicates. **P < 0.01 versus control RAFLSs. (GIF 6 kb)

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Supplementary Fig. 2

DMSO has no effects on RAFLS apoptosis. Human RAFLSs were cultured in the presence or absence of DMSO (0.01 %, v/v) for 72 h. Cell apoptosis was measured by annexin V and PI double staining. a Apoptotic cells are localized in the lower right (early apoptosis) and upper right (late apoptosis) quadrants of the dot-plot graph. b Quantitative analysis of annexin V positive cells by flow cytometry. The graphs represent typical results of cellular apoptosis. Values represent the mean ± SD of three independent experiments in triplicates. (GIF 21 kb)

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Chang, Yw., Zhao, Yf., Cao, Yl. et al. RETRACTED ARTICLE: Bufalin Exerts Inhibitory Effects on IL-1β-Mediated Proliferation and Induces Apoptosis in Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Inflammation 37, 1552–1559 (2014). https://doi.org/10.1007/s10753-014-9882-5

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