Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activationReportar como inadecuado




Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Translational Medicine

, 13:91

First Online: 15 March 2015Received: 25 September 2014Accepted: 17 February 2015DOI: 10.1186-s12967-015-0440-1

Cite this article as: Kong, X., Wu, W., Yang, Y. et al. J Transl Med 2015 13: 91. doi:10.1186-s12967-015-0440-1

Abstract

Osteoclasts, bone-specialized multinucleated cells, are responsible for bone destructive diseases such as rheumatoid arthritis and osteoporosis. Natural plant-derived products have received substantial attention given their potential therapeutic and preventive activities against bone destructive diseases. In the present study, we investigated the effects of total saponin TS from Anemone flaccida Fr. Schmidt, on receptor activator of nuclear factor-κB ligand RANKL-induced in vitro osteoclast differentiation. We observed that TS concentration-dependently inhibited RANKL-induced osteoclast formation from RAW 264.7 cell and bone marrow-derived macrophages BMMs, as well as decreased extent of actin ring formation and lacunar resorption. The RANKL-stimulated expression of osteoclast-related transcription factors were also diminished by TS. Moreover, TS blocked the RANKL-triggered TRAF6 expression, phosphorylation of mitogen-activated protein kinases MAPKs and IκB-α, and inhibited NF-κB p65 DNA binding activity. Furthermore, TS almost abrogated the nuclear factor of activated T cells NFATc1 and c-Fos expression. Taken together, our results demonstrated that TS suppresses RANKL-induced osteoclast differentiation and inflammatory bone loss via the down-regulation of TRAF6 level, suppression of JNK and p38 MAPKs and NF-κB activation, and subsequent decreased expression of c-Fos and NFATc1. Therefore, TS may be a potential agent and needs to be more evaluated in vivo or in clinical trials to become a therapeutic for lytic bone diseases.

KeywordsAnemone flaccida RANKL Osteoclasts Bone resorption MAPKs NF-κB Electronic supplementary materialThe online version of this article doi:10.1186-s12967-015-0440-1 contains supplementary material, which is available to authorized users.

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Autor: Xiangying Kong - Wenbin Wu - Yue Yang - Hongye Wan - Xiaomin Li - Michun Zhong - Hongyan Zhao - Xiaohui Su - Shiwei Jia -

Fuente: https://link.springer.com/







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