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A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia

OBJECTIVES: A20 exerts an anti‐osteoclastogenic effect through the inhibition of NF‐κB signalling in periodontitis. It also regulates autophagy via ubiquitin modification. This study was aimed at exploring the relationship between A20 and autophagy in anti‐osteoclastogenesis in human periodontal lig...

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Autores principales: Yan, Ke, Wu, Chengyu, Ye, Yu, Li, Lu, Wang, Xiaoqian, He, Wei, Ren, Shuangshuang, Xu, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106956/
https://www.ncbi.nlm.nih.gov/pubmed/32027437
http://dx.doi.org/10.1111/cpr.12778
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author Yan, Ke
Wu, Chengyu
Ye, Yu
Li, Lu
Wang, Xiaoqian
He, Wei
Ren, Shuangshuang
Xu, Yan
author_facet Yan, Ke
Wu, Chengyu
Ye, Yu
Li, Lu
Wang, Xiaoqian
He, Wei
Ren, Shuangshuang
Xu, Yan
author_sort Yan, Ke
collection PubMed
description OBJECTIVES: A20 exerts an anti‐osteoclastogenic effect through the inhibition of NF‐κB signalling in periodontitis. It also regulates autophagy via ubiquitin modification. This study was aimed at exploring the relationship between A20 and autophagy in anti‐osteoclastogenesis in human periodontal ligament cells (hPDLCs) under hypoxia. MATERIALS AND METHODS: Real‐time PCR and Western blot were used to detect relative mRNA and protein levels. The formation of autophagosomes was measured by TEM. Osteoclastic differentiation was assessed by TRAP staining and hydroxyapatite resorption assay. The interactions between different proteins were observed by co‐IP. RESULTS: Cells cultured under 2% O₂ exhibited decreased A20 expression and increased RANKL/OPG (R/O) ratio. There was a negative correlation between A20 and TRAF6, and similar results were found with autophagic flux. A20 delayed the increase in R/O ratio under hypoxia. Autophagy in hPDLCs and osteoclast differentiation and hydroxyapatite resorption areas in mouse bone marrow mononuclear cells (BMMCs) were inhibited by A20. Moreover, inhibition of autophagy using 3‐MA resulted in increased expression of A20 and decreased number and function of osteoclasts. In addition, A20 inhibited polyubiquitination at K63 and enhanced that at K48 in TRAF6 to suppress autophagy under hypoxic conditions. CONCLUSIONS: A20 inhibits osteoclastogenesis via inhibition of TRAF6‐dependent autophagy in hPDLCs under hypoxia. These findings suggest that A20 may be a key gene target during bone loss in periodontitis via TRAF6‐mediated inhibition of autophagy.
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spelling pubmed-71069562020-04-01 A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia Yan, Ke Wu, Chengyu Ye, Yu Li, Lu Wang, Xiaoqian He, Wei Ren, Shuangshuang Xu, Yan Cell Prolif Original Articles OBJECTIVES: A20 exerts an anti‐osteoclastogenic effect through the inhibition of NF‐κB signalling in periodontitis. It also regulates autophagy via ubiquitin modification. This study was aimed at exploring the relationship between A20 and autophagy in anti‐osteoclastogenesis in human periodontal ligament cells (hPDLCs) under hypoxia. MATERIALS AND METHODS: Real‐time PCR and Western blot were used to detect relative mRNA and protein levels. The formation of autophagosomes was measured by TEM. Osteoclastic differentiation was assessed by TRAP staining and hydroxyapatite resorption assay. The interactions between different proteins were observed by co‐IP. RESULTS: Cells cultured under 2% O₂ exhibited decreased A20 expression and increased RANKL/OPG (R/O) ratio. There was a negative correlation between A20 and TRAF6, and similar results were found with autophagic flux. A20 delayed the increase in R/O ratio under hypoxia. Autophagy in hPDLCs and osteoclast differentiation and hydroxyapatite resorption areas in mouse bone marrow mononuclear cells (BMMCs) were inhibited by A20. Moreover, inhibition of autophagy using 3‐MA resulted in increased expression of A20 and decreased number and function of osteoclasts. In addition, A20 inhibited polyubiquitination at K63 and enhanced that at K48 in TRAF6 to suppress autophagy under hypoxic conditions. CONCLUSIONS: A20 inhibits osteoclastogenesis via inhibition of TRAF6‐dependent autophagy in hPDLCs under hypoxia. These findings suggest that A20 may be a key gene target during bone loss in periodontitis via TRAF6‐mediated inhibition of autophagy. John Wiley and Sons Inc. 2020-02-06 /pmc/articles/PMC7106956/ /pubmed/32027437 http://dx.doi.org/10.1111/cpr.12778 Text en © 2020 The Authors. Cell Proliferation Published by 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
Yan, Ke
Wu, Chengyu
Ye, Yu
Li, Lu
Wang, Xiaoqian
He, Wei
Ren, Shuangshuang
Xu, Yan
A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia
title A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia
title_full A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia
title_fullStr A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia
title_full_unstemmed A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia
title_short A20 inhibits osteoclastogenesis via TRAF6‐dependent autophagy in human periodontal ligament cells under hypoxia
title_sort a20 inhibits osteoclastogenesis via traf6‐dependent autophagy in human periodontal ligament cells under hypoxia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106956/
https://www.ncbi.nlm.nih.gov/pubmed/32027437
http://dx.doi.org/10.1111/cpr.12778
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