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Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages
Inflammation can promote the maturity of osteoclasts and bone resorption in many bone disease such as osteoporosis and arthritis. Here, we aimed to investigate the inhibitory effects of deacylcynaropicrin (DAC) on osteoclastogenesis and bone resorption induced by RANKL. Bone-marrow-derived macrophag...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567936/ https://www.ncbi.nlm.nih.gov/pubmed/31231214 http://dx.doi.org/10.3389/fphar.2019.00599 |
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author | Li, Zhikun Zhu, Xiaodong Xu, Ruijun Wang, Yi Hu, Ruixi Xu, Wei |
author_facet | Li, Zhikun Zhu, Xiaodong Xu, Ruijun Wang, Yi Hu, Ruixi Xu, Wei |
author_sort | Li, Zhikun |
collection | PubMed |
description | Inflammation can promote the maturity of osteoclasts and bone resorption in many bone disease such as osteoporosis and arthritis. Here, we aimed to investigate the inhibitory effects of deacylcynaropicrin (DAC) on osteoclastogenesis and bone resorption induced by RANKL. Bone-marrow-derived macrophages were used for assessing the influence of DAC on polarization of macrophages and osteoclastogenesis in vitro. Inducible nitric oxide synthase (iNOS) and CD206, as well as osteoclastogenesis markers, nuclear factor of activated T-cells 1 (NFATc1), and c-Fos, were qualitatively analyzed by immunofluorescence, flow cytometry, reverse transcription polymerase chain reaction, and Western blotting. The results showed that DAC significantly inhibited osteoclastogenesis by suppressing the expression levels of c-Fos and NFATc1 through nuclear factor-κB, c-Jun N-terminal kinase (JNK), and Akt pathway. Moreover, immunohistochemistry and enzyme-linked immunosorbent assays showed that DAC reduced the release of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in vivo. Finally, DAC also promoted macrophage polarization from M1 to M2 types. In conclusion, these results demonstrated that DAC suppressed RANKL-induced inflammation and osteoclastogenesis and therefore it can be used as a potential treatment for osteoporosis, arthritis, osteolysis, and aseptic loosening of artificial prostheses. |
format | Online Article Text |
id | pubmed-6567936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65679362019-06-21 Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages Li, Zhikun Zhu, Xiaodong Xu, Ruijun Wang, Yi Hu, Ruixi Xu, Wei Front Pharmacol Pharmacology Inflammation can promote the maturity of osteoclasts and bone resorption in many bone disease such as osteoporosis and arthritis. Here, we aimed to investigate the inhibitory effects of deacylcynaropicrin (DAC) on osteoclastogenesis and bone resorption induced by RANKL. Bone-marrow-derived macrophages were used for assessing the influence of DAC on polarization of macrophages and osteoclastogenesis in vitro. Inducible nitric oxide synthase (iNOS) and CD206, as well as osteoclastogenesis markers, nuclear factor of activated T-cells 1 (NFATc1), and c-Fos, were qualitatively analyzed by immunofluorescence, flow cytometry, reverse transcription polymerase chain reaction, and Western blotting. The results showed that DAC significantly inhibited osteoclastogenesis by suppressing the expression levels of c-Fos and NFATc1 through nuclear factor-κB, c-Jun N-terminal kinase (JNK), and Akt pathway. Moreover, immunohistochemistry and enzyme-linked immunosorbent assays showed that DAC reduced the release of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in vivo. Finally, DAC also promoted macrophage polarization from M1 to M2 types. In conclusion, these results demonstrated that DAC suppressed RANKL-induced inflammation and osteoclastogenesis and therefore it can be used as a potential treatment for osteoporosis, arthritis, osteolysis, and aseptic loosening of artificial prostheses. Frontiers Media S.A. 2019-06-07 /pmc/articles/PMC6567936/ /pubmed/31231214 http://dx.doi.org/10.3389/fphar.2019.00599 Text en Copyright © 2019 Li, Zhu, Xu, Wang, Hu and Xu http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Li, Zhikun Zhu, Xiaodong Xu, Ruijun Wang, Yi Hu, Ruixi Xu, Wei Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages |
title | Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages |
title_full | Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages |
title_fullStr | Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages |
title_full_unstemmed | Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages |
title_short | Deacylcynaropicrin Inhibits RANKL-Induced Osteoclastogenesis by Inhibiting NF-κB and MAPK and Promoting M2 Polarization of Macrophages |
title_sort | deacylcynaropicrin inhibits rankl-induced osteoclastogenesis by inhibiting nf-κb and mapk and promoting m2 polarization of macrophages |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567936/ https://www.ncbi.nlm.nih.gov/pubmed/31231214 http://dx.doi.org/10.3389/fphar.2019.00599 |
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