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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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1179007/full |
| _version_ | 1797844988249243648 |
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| author | Tsukasa Aoki Tsukasa Aoki Fumitaka Hiura Aonan Li Nan Yang Nana Takakura-Hino Satoru Mukai Miho Matsuda Fusanori Nishimura Eijiro Jimi Eijiro Jimi |
| author_facet | Tsukasa Aoki Tsukasa Aoki Fumitaka Hiura Aonan Li Nan Yang Nana Takakura-Hino Satoru Mukai Miho Matsuda Fusanori Nishimura Eijiro Jimi Eijiro Jimi |
| author_sort | Tsukasa Aoki |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-09T17:31:18Z |
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| id | doaj.art-4b93d59247924d6b8bfa6919605f0ab6 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T17:31:18Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-4b93d59247924d6b8bfa6919605f0ab62023-04-18T04:58:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11790071179007Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone lossTsukasa Aoki0Tsukasa Aoki1Fumitaka Hiura2Aonan Li3Nan Yang4Nana Takakura-Hino5Satoru Mukai6Miho Matsuda7Fusanori Nishimura8Eijiro Jimi9Eijiro Jimi10Laboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanDepartment of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, JapanLaboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanLaboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanLaboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanLaboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanDepartment of Health and Nutrition Care, Faculty of Allied Health Sciences, University of East Asia, Shimonoseki, JapanLaboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanDepartment of Periodontology, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, JapanLaboratory of Molecular and Cellular Biochemistry, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, Fukuoka, JapanOral Health/Brain Health/Total Health Research Center, Faculty of Dental Science, Kyushu University, Fukuoka, JapanPeriodontal 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1179007/fullnuclear factor-k Bperiodonititisosteoclasts (OCs)inflammationboneNIK |
| spellingShingle | Tsukasa Aoki Tsukasa Aoki Fumitaka Hiura Aonan Li Nan Yang Nana Takakura-Hino Satoru Mukai Miho Matsuda Fusanori Nishimura Eijiro Jimi Eijiro Jimi Inhibition of non-canonical NF-κB signaling suppresses periodontal inflammation and bone loss Frontiers in Immunology nuclear factor-k B periodonititis osteoclasts (OCs) inflammation bone NIK |
| 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 | nuclear factor-k B periodonititis osteoclasts (OCs) inflammation bone NIK |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1179007/full |
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