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Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption

Inflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction. As a specialized inflammatory pathological process, dental internal resorption (IR) includes both soft and hard tissues deconstruction within the dentin-pulp complex, which has been one...

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Autores principales: Yu, Fanyuan, Huo, Fengli, Li, Feifei, Zuo, Yanqin, Wang, Chenglin, Ye, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791990/
https://www.ncbi.nlm.nih.gov/pubmed/35082271
http://dx.doi.org/10.1038/s41368-022-00159-3
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author Yu, Fanyuan
Huo, Fengli
Li, Feifei
Zuo, Yanqin
Wang, Chenglin
Ye, Ling
author_facet Yu, Fanyuan
Huo, Fengli
Li, Feifei
Zuo, Yanqin
Wang, Chenglin
Ye, Ling
author_sort Yu, Fanyuan
collection PubMed
description Inflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction. As a specialized inflammatory pathological process, dental internal resorption (IR) includes both soft and hard tissues deconstruction within the dentin-pulp complex, which has been one of the main reasons for inflammatory tooth loss. Mechanisms of inflammatory matrix degradation and tissue resorption in IR are largely unclear. In this study, we used a combination of Cre-loxP reporter, flow cytometry, cell transplantation, and enzyme activities assay to mechanistically investigate the role of regenerative cells, odontoblasts (ODs), in inflammatory mineral resorption and matrices degradation. We report that inflamed ODs have strong capabilities of matrix degradation and tissue resorption. Traditionally, ODs are regarded as hard-tissue regenerative cells; however, our data unexpectedly present ODs as a crucial population that participates in IR-associated tissue deconstruction. Specifically, we uncovered that nuclear factor-kappa b (NF-κB) signaling orchestrated Tumor necrosis factor α (TNF-α)-induced matrix metalloproteinases (Mmps) and Cathepsin K (Ctsk) functions in ODs to enhance matrix degradation and tissue resorption. Furthermore, TNF-α increases Rankl/Opg ratio in ODs via NF-κB signaling by impairing Opg expression but increasing Rankl level, which utterly makes ODs cell line 17IIA11 (A11) become Trap(+) and Ctsk(+) multinucleated cells to perform resorptive actions. Blocking of NF-κB signaling significantly rescues matrix degradation and resorptive functions of inflamed ODs via repressing vital inflammatory proteinases Mmps and Ctsk. Utterly, via utilizing NF-κB specific small molecule inhibitors we satisfactorily attenuated inflammatory ODs-associated human dental IR in vivo. Our data reveal the underlying mechanisms of inflammatory matrix degradation and resorption via proteinase activities in IR-related pathological conditions.
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spelling pubmed-87919902022-02-07 Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption Yu, Fanyuan Huo, Fengli Li, Feifei Zuo, Yanqin Wang, Chenglin Ye, Ling Int J Oral Sci Article Inflammation-associated proteinase functions are key determinants of inflammatory stromal tissues deconstruction. As a specialized inflammatory pathological process, dental internal resorption (IR) includes both soft and hard tissues deconstruction within the dentin-pulp complex, which has been one of the main reasons for inflammatory tooth loss. Mechanisms of inflammatory matrix degradation and tissue resorption in IR are largely unclear. In this study, we used a combination of Cre-loxP reporter, flow cytometry, cell transplantation, and enzyme activities assay to mechanistically investigate the role of regenerative cells, odontoblasts (ODs), in inflammatory mineral resorption and matrices degradation. We report that inflamed ODs have strong capabilities of matrix degradation and tissue resorption. Traditionally, ODs are regarded as hard-tissue regenerative cells; however, our data unexpectedly present ODs as a crucial population that participates in IR-associated tissue deconstruction. Specifically, we uncovered that nuclear factor-kappa b (NF-κB) signaling orchestrated Tumor necrosis factor α (TNF-α)-induced matrix metalloproteinases (Mmps) and Cathepsin K (Ctsk) functions in ODs to enhance matrix degradation and tissue resorption. Furthermore, TNF-α increases Rankl/Opg ratio in ODs via NF-κB signaling by impairing Opg expression but increasing Rankl level, which utterly makes ODs cell line 17IIA11 (A11) become Trap(+) and Ctsk(+) multinucleated cells to perform resorptive actions. Blocking of NF-κB signaling significantly rescues matrix degradation and resorptive functions of inflamed ODs via repressing vital inflammatory proteinases Mmps and Ctsk. Utterly, via utilizing NF-κB specific small molecule inhibitors we satisfactorily attenuated inflammatory ODs-associated human dental IR in vivo. Our data reveal the underlying mechanisms of inflammatory matrix degradation and resorption via proteinase activities in IR-related pathological conditions. Nature Publishing Group UK 2022-01-26 /pmc/articles/PMC8791990/ /pubmed/35082271 http://dx.doi.org/10.1038/s41368-022-00159-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Yu, Fanyuan
Huo, Fengli
Li, Feifei
Zuo, Yanqin
Wang, Chenglin
Ye, Ling
Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
title Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
title_full Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
title_fullStr Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
title_full_unstemmed Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
title_short Aberrant NF-κB activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
title_sort aberrant nf-κb activation in odontoblasts orchestrates inflammatory matrix degradation and mineral resorption
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791990/
https://www.ncbi.nlm.nih.gov/pubmed/35082271
http://dx.doi.org/10.1038/s41368-022-00159-3
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