Cargando…

Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression

Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-κB) signaling pathways...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Hyerim, Lee, Kyubin, Lee, Sheunghun, Lee, Jisu, Jeong, Won Tae, Lim, Heung Bin, Hyun, Tae Kyung, Yi, Sun-Ju, Kim, Kyunghwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072883/
https://www.ncbi.nlm.nih.gov/pubmed/32079267
http://dx.doi.org/10.3390/ijms21041347
_version_ 1783506510175797248
author Lee, Hyerim
Lee, Kyubin
Lee, Sheunghun
Lee, Jisu
Jeong, Won Tae
Lim, Heung Bin
Hyun, Tae Kyung
Yi, Sun-Ju
Kim, Kyunghwan
author_facet Lee, Hyerim
Lee, Kyubin
Lee, Sheunghun
Lee, Jisu
Jeong, Won Tae
Lim, Heung Bin
Hyun, Tae Kyung
Yi, Sun-Ju
Kim, Kyunghwan
author_sort Lee, Hyerim
collection PubMed
description Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-κB) signaling pathways in response to receptor activation of NF-κB ligand (RANKL). Since excessive RANKL signaling causes an increase of osteoclast formation and bone resorption, inhibition of RANKL or its signaling pathway is an attractive therapeutic approach to the treatment of pathologic bone loss. In this study, we show that an ethyl acetate fraction (LEA) from the shiitake mushroom, Lentinula edodes, inhibited RANKL-induced osteoclast differentiation by blocking the NFATc1 signaling pathway. We found that the water extract and its subsequent ethyl acetate fraction of L. edodes significantly suppressed osteoclast formation. Comparative transcriptome analysis revealed that LEA specifically downregulated a set of RANKL target genes, including Nfatc1. Next, we found that LEA suppresses Nfatc1 expression mainly through the inhibition of the transactivity of p65 and NFATc1. Moreover, treatment of LEA rescued an osteoporotic phenotype in a zebrafish model of glucocorticoid-induced osteoporosis. Collectively, our findings define an undocumented role of the shiitake mushroom extract in regulating bone development.
format Online
Article
Text
id pubmed-7072883
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70728832020-03-19 Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression Lee, Hyerim Lee, Kyubin Lee, Sheunghun Lee, Jisu Jeong, Won Tae Lim, Heung Bin Hyun, Tae Kyung Yi, Sun-Ju Kim, Kyunghwan Int J Mol Sci Article Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-κB) signaling pathways in response to receptor activation of NF-κB ligand (RANKL). Since excessive RANKL signaling causes an increase of osteoclast formation and bone resorption, inhibition of RANKL or its signaling pathway is an attractive therapeutic approach to the treatment of pathologic bone loss. In this study, we show that an ethyl acetate fraction (LEA) from the shiitake mushroom, Lentinula edodes, inhibited RANKL-induced osteoclast differentiation by blocking the NFATc1 signaling pathway. We found that the water extract and its subsequent ethyl acetate fraction of L. edodes significantly suppressed osteoclast formation. Comparative transcriptome analysis revealed that LEA specifically downregulated a set of RANKL target genes, including Nfatc1. Next, we found that LEA suppresses Nfatc1 expression mainly through the inhibition of the transactivity of p65 and NFATc1. Moreover, treatment of LEA rescued an osteoporotic phenotype in a zebrafish model of glucocorticoid-induced osteoporosis. Collectively, our findings define an undocumented role of the shiitake mushroom extract in regulating bone development. MDPI 2020-02-17 /pmc/articles/PMC7072883/ /pubmed/32079267 http://dx.doi.org/10.3390/ijms21041347 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Hyerim
Lee, Kyubin
Lee, Sheunghun
Lee, Jisu
Jeong, Won Tae
Lim, Heung Bin
Hyun, Tae Kyung
Yi, Sun-Ju
Kim, Kyunghwan
Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression
title Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression
title_full Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression
title_fullStr Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression
title_full_unstemmed Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression
title_short Ethyl Acetate Fraction of Aqueous Extract of Lentinula edodes Inhibits Osteoclastogenesis by Suppressing NFATc1 Expression
title_sort ethyl acetate fraction of aqueous extract of lentinula edodes inhibits osteoclastogenesis by suppressing nfatc1 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072883/
https://www.ncbi.nlm.nih.gov/pubmed/32079267
http://dx.doi.org/10.3390/ijms21041347
work_keys_str_mv AT leehyerim ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT leekyubin ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT leesheunghun ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT leejisu ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT jeongwontae ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT limheungbin ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT hyuntaekyung ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT yisunju ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression
AT kimkyunghwan ethylacetatefractionofaqueousextractoflentinulaedodesinhibitsosteoclastogenesisbysuppressingnfatc1expression