Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Zhikun, Zhu, Xiaodong, Xu, Ruijun, Wang, Yi, Hu, Ruixi, Xu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
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
_version_ 1783427183700606976
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
work_keys_str_mv AT lizhikun deacylcynaropicrininhibitsranklinducedosteoclastogenesisbyinhibitingnfkbandmapkandpromotingm2polarizationofmacrophages
AT zhuxiaodong deacylcynaropicrininhibitsranklinducedosteoclastogenesisbyinhibitingnfkbandmapkandpromotingm2polarizationofmacrophages
AT xuruijun deacylcynaropicrininhibitsranklinducedosteoclastogenesisbyinhibitingnfkbandmapkandpromotingm2polarizationofmacrophages
AT wangyi deacylcynaropicrininhibitsranklinducedosteoclastogenesisbyinhibitingnfkbandmapkandpromotingm2polarizationofmacrophages
AT huruixi deacylcynaropicrininhibitsranklinducedosteoclastogenesisbyinhibitingnfkbandmapkandpromotingm2polarizationofmacrophages
AT xuwei deacylcynaropicrininhibitsranklinducedosteoclastogenesisbyinhibitingnfkbandmapkandpromotingm2polarizationofmacrophages