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Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis
BACKGROUND: Artificial joint replacement surgery is often accompanied by osteolysis induced aseptic loosening around the prosthesis. Wear particles from joint replacement are thought to be one of the main factors leading to local inflammation and osteolysis at the prosthesis site. The aim of this st...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048890/ https://www.ncbi.nlm.nih.gov/pubmed/33386763 http://dx.doi.org/10.1002/cbin.11544 |
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author | Wang, Lei Gao, Zhibiao Zhang, Jie Huo, Yulong Xu, Qiang Qiu, Yusheng |
author_facet | Wang, Lei Gao, Zhibiao Zhang, Jie Huo, Yulong Xu, Qiang Qiu, Yusheng |
author_sort | Wang, Lei |
collection | PubMed |
description | BACKGROUND: Artificial joint replacement surgery is often accompanied by osteolysis induced aseptic loosening around the prosthesis. Wear particles from joint replacement are thought to be one of the main factors leading to local inflammation and osteolysis at the prosthesis site. The aim of this study was to investigate the molecular mechanism of osteoclast formation and dissolution induced by wear particles and the potential roles of Netrin‐1, the ERK1/2 pathway and autophagy activation in this process. METHODS: The messenger RNA levels in cells and tissues were detected with real‐time quantitative PCR. The western blotting was used to detect the expression of proteins. A CCK‐8 kit was used to detect the viability of RAW 264.7 cells. Moreover, an air pouch model of bone resorption was established. Immunohistochemistry was used to detect the expression of TRAP and Netrin‐1 in rat bone tissue. Cell culture supernatants were collected in the rat air pouch model of bone resorption, and the levels of RANKL and OPG were detected with enzyme‐linked immunosorbent assay. The protein levels of TRAP and Netrin‐1 in bone tissue were examined by immunohistochemistry. RESULTS: Titanium wear particles induced osteoclast formation and autophagy activation. Moreover, blocking autophagy suppressed the osteoclastogenesis after exposure to wear particles in vitro. The activation of the ERK1/2 pathway and the overexpression of Netrin‐1 were both found to play important roles in osteoclastogenesis mediated by autophagy. Moreover, 3‐MA effectively decreased the secretion of proinflammatory cytokines mediated by wear particles. CONCLUSION: Blockade of autophagy inhibits the osteoclastogenesis and inflammation induced by wear particles, thus potentially providing novel treatment strategies for abnormal osteoclastogenesis and aseptic prosthesis loosening induced by wear particles. |
format | Online Article Text |
id | pubmed-8048890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80488902021-04-20 Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis Wang, Lei Gao, Zhibiao Zhang, Jie Huo, Yulong Xu, Qiang Qiu, Yusheng Cell Biol Int Regular Issue BACKGROUND: Artificial joint replacement surgery is often accompanied by osteolysis induced aseptic loosening around the prosthesis. Wear particles from joint replacement are thought to be one of the main factors leading to local inflammation and osteolysis at the prosthesis site. The aim of this study was to investigate the molecular mechanism of osteoclast formation and dissolution induced by wear particles and the potential roles of Netrin‐1, the ERK1/2 pathway and autophagy activation in this process. METHODS: The messenger RNA levels in cells and tissues were detected with real‐time quantitative PCR. The western blotting was used to detect the expression of proteins. A CCK‐8 kit was used to detect the viability of RAW 264.7 cells. Moreover, an air pouch model of bone resorption was established. Immunohistochemistry was used to detect the expression of TRAP and Netrin‐1 in rat bone tissue. Cell culture supernatants were collected in the rat air pouch model of bone resorption, and the levels of RANKL and OPG were detected with enzyme‐linked immunosorbent assay. The protein levels of TRAP and Netrin‐1 in bone tissue were examined by immunohistochemistry. RESULTS: Titanium wear particles induced osteoclast formation and autophagy activation. Moreover, blocking autophagy suppressed the osteoclastogenesis after exposure to wear particles in vitro. The activation of the ERK1/2 pathway and the overexpression of Netrin‐1 were both found to play important roles in osteoclastogenesis mediated by autophagy. Moreover, 3‐MA effectively decreased the secretion of proinflammatory cytokines mediated by wear particles. CONCLUSION: Blockade of autophagy inhibits the osteoclastogenesis and inflammation induced by wear particles, thus potentially providing novel treatment strategies for abnormal osteoclastogenesis and aseptic prosthesis loosening induced by wear particles. John Wiley and Sons Inc. 2021-01-13 2021-03 /pmc/articles/PMC8048890/ /pubmed/33386763 http://dx.doi.org/10.1002/cbin.11544 Text en © 2021 The Authors. Cell Biology International published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Regular Issue Wang, Lei Gao, Zhibiao Zhang, Jie Huo, Yulong Xu, Qiang Qiu, Yusheng Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
title | Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
title_full | Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
title_fullStr | Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
title_full_unstemmed | Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
title_short | Netrin‐1 regulates ERK1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
title_sort | netrin‐1 regulates erk1/2 signaling pathway and autophagy activation in wear particle‐induced osteoclastogenesis |
topic | Regular Issue |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048890/ https://www.ncbi.nlm.nih.gov/pubmed/33386763 http://dx.doi.org/10.1002/cbin.11544 |
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