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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...

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Autores principales: Aoki, Tsukasa, Hiura, Fumitaka, Li, Aonan, Yang, Nan, Takakura-Hino, Nana, Mukai, Satoru, Matsuda, Miho, Nishimura, Fusanori, Jimi, Eijiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
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.
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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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