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Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss
Periodontal disease is an infectious disease that affects many people worldwide. Disease progression destroys the alveolar bone and causes tooth loss. We have previously shown that alymphoplasia (aly/aly) mice harboring a loss-of-function mutation in the map3k14 gene, which is involved in p100 to p5...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151688/ https://www.ncbi.nlm.nih.gov/pubmed/37143646 http://dx.doi.org/10.3389/fimmu.2023.1179007 |
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author | Aoki, Tsukasa Hiura, Fumitaka Li, Aonan Yang, Nan Takakura-Hino, Nana Mukai, Satoru Matsuda, Miho Nishimura, Fusanori Jimi, Eijiro |
author_facet | Aoki, Tsukasa Hiura, Fumitaka Li, Aonan Yang, Nan Takakura-Hino, Nana Mukai, Satoru Matsuda, Miho Nishimura, Fusanori Jimi, Eijiro |
author_sort | Aoki, Tsukasa |
collection | PubMed |
description | Periodontal disease is an infectious disease that affects many people worldwide. Disease progression destroys the alveolar bone and causes tooth loss. We have previously shown that alymphoplasia (aly/aly) mice harboring a loss-of-function mutation in the map3k14 gene, which is involved in p100 to p52 processing of the alternative NF-κB pathway, exhibited mild osteopetrosis due to decreased number of osteoclasts, suggesting the alternative NF-κB pathway as a potential drug target for the amelioration of bone disease. In the present study, wild-type (WT) and aly/aly mice were subjected to silk ligation to establish a periodontitis model. Alveolar bone resorption was suppressed in aly/aly mice by decreased numbers of osteoclasts in the alveolar bone in comparison to WT mice. Furthermore, the expression of receptor activator of NF-κB ligand (RANKL) and TNFα (cytokines involved in osteoclast induction in periligative gingival tissue) was decreased. When primary osteoblasts (POBs) and bone marrow cells (BMCs) derived from WT and aly/aly mice were prepared and co-cultured, osteoclasts were induced from WT-derived BMCs, regardless of the origin of the POBs, but hardly formed from aly/aly mouse-derived BMCs. Furthermore, the local administration of an NIK inhibitor, Cpd33, inhibited osteoclast formation and thereby inhibited alveolar bone resorption in the periodontitis model. Therefore, the NIK-mediated NF-κB alternative pathway can be a therapeutic target for periodontal disease. |
format | Online Article Text |
id | pubmed-10151688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101516882023-05-03 Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss Aoki, Tsukasa Hiura, Fumitaka Li, Aonan Yang, Nan Takakura-Hino, Nana Mukai, Satoru Matsuda, Miho Nishimura, Fusanori Jimi, Eijiro Front Immunol Immunology Periodontal disease is an infectious disease that affects many people worldwide. Disease progression destroys the alveolar bone and causes tooth loss. We have previously shown that alymphoplasia (aly/aly) mice harboring a loss-of-function mutation in the map3k14 gene, which is involved in p100 to p52 processing of the alternative NF-κB pathway, exhibited mild osteopetrosis due to decreased number of osteoclasts, suggesting the alternative NF-κB pathway as a potential drug target for the amelioration of bone disease. In the present study, wild-type (WT) and aly/aly mice were subjected to silk ligation to establish a periodontitis model. Alveolar bone resorption was suppressed in aly/aly mice by decreased numbers of osteoclasts in the alveolar bone in comparison to WT mice. Furthermore, the expression of receptor activator of NF-κB ligand (RANKL) and TNFα (cytokines involved in osteoclast induction in periligative gingival tissue) was decreased. When primary osteoblasts (POBs) and bone marrow cells (BMCs) derived from WT and aly/aly mice were prepared and co-cultured, osteoclasts were induced from WT-derived BMCs, regardless of the origin of the POBs, but hardly formed from aly/aly mouse-derived BMCs. Furthermore, the local administration of an NIK inhibitor, Cpd33, inhibited osteoclast formation and thereby inhibited alveolar bone resorption in the periodontitis model. Therefore, the NIK-mediated NF-κB alternative pathway can be a therapeutic target for periodontal disease. Frontiers Media S.A. 2023-04-18 /pmc/articles/PMC10151688/ /pubmed/37143646 http://dx.doi.org/10.3389/fimmu.2023.1179007 Text en Copyright © 2023 Aoki, Hiura, Li, Yang, Takakura-Hino, Mukai, Matsuda, Nishimura and Jimi 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 | Immunology Aoki, Tsukasa Hiura, Fumitaka Li, Aonan Yang, Nan Takakura-Hino, Nana Mukai, Satoru Matsuda, Miho Nishimura, Fusanori Jimi, Eijiro Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss |
title | Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss |
title_full | Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss |
title_fullStr | Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss |
title_full_unstemmed | Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss |
title_short | Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss |
title_sort | inhibition of non-canonical nf-κb signaling suppresses periodontal inflammation and bone loss |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10151688/ https://www.ncbi.nlm.nih.gov/pubmed/37143646 http://dx.doi.org/10.3389/fimmu.2023.1179007 |
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