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TRAF-STOP alleviates osteoclastogenesis in periodontitis
The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inf...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229065/ https://www.ncbi.nlm.nih.gov/pubmed/37261283 http://dx.doi.org/10.3389/fphar.2023.1119847 |
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author | Huang, Yaxian Wu, Jinyan Zhan, Chi Liu, Rong Zhou, Zhaocai Huang, Xin Tian, Yaguang Lin, Zhengmei Song, Zhi |
author_facet | Huang, Yaxian Wu, Jinyan Zhan, Chi Liu, Rong Zhou, Zhaocai Huang, Xin Tian, Yaguang Lin, Zhengmei Song, Zhi |
author_sort | Huang, Yaxian |
collection | PubMed |
description | The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis. |
format | Online Article Text |
id | pubmed-10229065 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102290652023-05-31 TRAF-STOP alleviates osteoclastogenesis in periodontitis Huang, Yaxian Wu, Jinyan Zhan, Chi Liu, Rong Zhou, Zhaocai Huang, Xin Tian, Yaguang Lin, Zhengmei Song, Zhi Front Pharmacol Pharmacology The enhanced osteoclastogenesis contributes to alveolar bone resorption in periodontitis, which increases the risk of tooth loss. To reduce bone destruction, the inhibition of osteoclast development is proposed as a feasible treatment. CD40L-CD40-TRAF6 signal transduction plays a crucial role in inflammation, but how it regulates osteoclast activity in periodontitis has not been elucidated. In this study, we showed the potential role of CD40L-CD40-TRAF6 signaling in periodontitis. CD40L obviously promoted osteoclast formation and bone resorption capacity in vitro. Mechanistically, we found that osteoclastogenesis was enhanced by the overexpression of NFATc1 and NF-κB activation. Importantly, osteoclast activity was effectively suppressed by TRAF-STOP, a small molecular inhibitor of TRAF6. Furthermore, local injection of TRAF-STOP-loaded injectable PLGA-PEG-PLGA hydrogel could alleviate ligation-induced periodontitis in vivo. Taken together, TRAF-STOP shows promising clinical efficacy in periodontitis through alleviating osteoclastogenesis. Frontiers Media S.A. 2023-05-15 /pmc/articles/PMC10229065/ /pubmed/37261283 http://dx.doi.org/10.3389/fphar.2023.1119847 Text en Copyright © 2023 Huang, Wu, Zhan, Liu, Zhou, Huang, Tian, Lin and Song. https://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 Huang, Yaxian Wu, Jinyan Zhan, Chi Liu, Rong Zhou, Zhaocai Huang, Xin Tian, Yaguang Lin, Zhengmei Song, Zhi TRAF-STOP alleviates osteoclastogenesis in periodontitis |
title | TRAF-STOP alleviates osteoclastogenesis in periodontitis |
title_full | TRAF-STOP alleviates osteoclastogenesis in periodontitis |
title_fullStr | TRAF-STOP alleviates osteoclastogenesis in periodontitis |
title_full_unstemmed | TRAF-STOP alleviates osteoclastogenesis in periodontitis |
title_short | TRAF-STOP alleviates osteoclastogenesis in periodontitis |
title_sort | traf-stop alleviates osteoclastogenesis in periodontitis |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229065/ https://www.ncbi.nlm.nih.gov/pubmed/37261283 http://dx.doi.org/10.3389/fphar.2023.1119847 |
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