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Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1
Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855823/ https://www.ncbi.nlm.nih.gov/pubmed/29463002 http://dx.doi.org/10.3390/ijms19020601 |
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author | Kim, Kiryeong Kim, Tae Hoon Ihn, Hye Jung Kim, Jung Eun Choi, Je-Yong Shin, Hong-In Park, Eui Kyun |
author_facet | Kim, Kiryeong Kim, Tae Hoon Ihn, Hye Jung Kim, Jung Eun Choi, Je-Yong Shin, Hong-In Park, Eui Kyun |
author_sort | Kim, Kiryeong |
collection | PubMed |
description | Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp). However, purpurogallin did not affect the bone resorbing function of mature osteoclasts evident by the resorption pit assay. Activation of mitogen-activated protein kinases, Akt and IkB pathways in RANK signaling were not altered by purpurogallin, whereas the expression of c-Fos and NFATc1, key transcriptional regulators in osteoclastogenesis, was dramatically inhibited by purpurogallin. Purpurogallin also significantly reduced the expression level of B lymphocyte-induced maturation protein-1 (Blimp1) gene (Prdm1). Further, downregulation of Blimp1 led to forced expression of anti-osteoclastogenic genes, including interferon regulatory factor-8 (Irf8) and B-cell lymphoma 6 (Bcl6) genes. Taken together, our data suggested that purpurogallin inhibits osteoclast differentiation via downregulation of c-Fos and NFATc1. |
format | Online Article Text |
id | pubmed-5855823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-58558232018-03-20 Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1 Kim, Kiryeong Kim, Tae Hoon Ihn, Hye Jung Kim, Jung Eun Choi, Je-Yong Shin, Hong-In Park, Eui Kyun Int J Mol Sci Article Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp). However, purpurogallin did not affect the bone resorbing function of mature osteoclasts evident by the resorption pit assay. Activation of mitogen-activated protein kinases, Akt and IkB pathways in RANK signaling were not altered by purpurogallin, whereas the expression of c-Fos and NFATc1, key transcriptional regulators in osteoclastogenesis, was dramatically inhibited by purpurogallin. Purpurogallin also significantly reduced the expression level of B lymphocyte-induced maturation protein-1 (Blimp1) gene (Prdm1). Further, downregulation of Blimp1 led to forced expression of anti-osteoclastogenic genes, including interferon regulatory factor-8 (Irf8) and B-cell lymphoma 6 (Bcl6) genes. Taken together, our data suggested that purpurogallin inhibits osteoclast differentiation via downregulation of c-Fos and NFATc1. MDPI 2018-02-17 /pmc/articles/PMC5855823/ /pubmed/29463002 http://dx.doi.org/10.3390/ijms19020601 Text en © 2018 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 Kim, Kiryeong Kim, Tae Hoon Ihn, Hye Jung Kim, Jung Eun Choi, Je-Yong Shin, Hong-In Park, Eui Kyun Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1 |
title | Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1 |
title_full | Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1 |
title_fullStr | Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1 |
title_full_unstemmed | Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1 |
title_short | Inhibitory Effect of Purpurogallin on Osteoclast Differentiation In Vitro through the Downregulation of c-Fos and NFATc1 |
title_sort | inhibitory effect of purpurogallin on osteoclast differentiation in vitro through the downregulation of c-fos and nfatc1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855823/ https://www.ncbi.nlm.nih.gov/pubmed/29463002 http://dx.doi.org/10.3390/ijms19020601 |
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