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Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy
Aseptic prosthetic loosening due to wear particle–induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro‐osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extens...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754000/ https://www.ncbi.nlm.nih.gov/pubmed/33135301 http://dx.doi.org/10.1111/jcmm.16055 |
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author | Chu, Binxiang Chen, Shenao Zheng, Xiaohe Ye, Jiajing Cheng, Xu Zhang, Liwei Guo, Di Wang, Peng Hong, Dun Hong, Zhenghua |
author_facet | Chu, Binxiang Chen, Shenao Zheng, Xiaohe Ye, Jiajing Cheng, Xu Zhang, Liwei Guo, Di Wang, Peng Hong, Dun Hong, Zhenghua |
author_sort | Chu, Binxiang |
collection | PubMed |
description | Aseptic prosthetic loosening due to wear particle–induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro‐osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extensive bone destruction around the bone‐implant interface. Here we showed that Nepetin, a natural bioactive flavonoid with proven anti‐inflammatory and anti‐proliferative properties, potently inhibited RANKL‐induced osteoclast differentiation, formation and bone resorption in vitro, and protected mice against the deleterious effects of titanium particle–induced calvarial osteolysis in vivo. Mechanistically, Nepetin attenuated RANKL‐induced activation of NF‐κB and MAPK signalling pathways and TRAF6‐dependent ubiquitination of Beclin 1 which is necessary for the induction of autophagy. In brief, our study demonstrates the potential therapeutic application of Nepetin against osteoclast‐mediated osteolytic diseases. |
format | Online Article Text |
id | pubmed-7754000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77540002020-12-23 Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy Chu, Binxiang Chen, Shenao Zheng, Xiaohe Ye, Jiajing Cheng, Xu Zhang, Liwei Guo, Di Wang, Peng Hong, Dun Hong, Zhenghua J Cell Mol Med Original Articles Aseptic prosthetic loosening due to wear particle–induced inflammatory osteolysis is the main cause of failure for artificial joint replacement. The inflammatory response and the production of pro‐osteoclastic factors lead to elevation of osteoclast formation and excessive activity results in extensive bone destruction around the bone‐implant interface. Here we showed that Nepetin, a natural bioactive flavonoid with proven anti‐inflammatory and anti‐proliferative properties, potently inhibited RANKL‐induced osteoclast differentiation, formation and bone resorption in vitro, and protected mice against the deleterious effects of titanium particle–induced calvarial osteolysis in vivo. Mechanistically, Nepetin attenuated RANKL‐induced activation of NF‐κB and MAPK signalling pathways and TRAF6‐dependent ubiquitination of Beclin 1 which is necessary for the induction of autophagy. In brief, our study demonstrates the potential therapeutic application of Nepetin against osteoclast‐mediated osteolytic diseases. John Wiley and Sons Inc. 2020-11-01 2020-12 /pmc/articles/PMC7754000/ /pubmed/33135301 http://dx.doi.org/10.1111/jcmm.16055 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Chu, Binxiang Chen, Shenao Zheng, Xiaohe Ye, Jiajing Cheng, Xu Zhang, Liwei Guo, Di Wang, Peng Hong, Dun Hong, Zhenghua Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy |
title | Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy |
title_full | Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy |
title_fullStr | Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy |
title_full_unstemmed | Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy |
title_short | Nepetin inhibits osteoclastogenesis by inhibiting RANKL‐induced activation of NF‐κB and MAPK signalling pathway, and autophagy |
title_sort | nepetin inhibits osteoclastogenesis by inhibiting rankl‐induced activation of nf‐κb and mapk signalling pathway, and autophagy |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754000/ https://www.ncbi.nlm.nih.gov/pubmed/33135301 http://dx.doi.org/10.1111/jcmm.16055 |
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