{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:25:07Z","timestamp":1793147107824,"version":"4.5.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T00:00:00Z","timestamp":1681776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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 (<jats:italic>aly\/aly<\/jats:italic>) mice harboring a loss-of-function mutation in the <jats:italic>map3k14<\/jats:italic> gene, which is involved in p100 to p52 processing of the alternative NF-\u03baB pathway, exhibited mild osteopetrosis due to decreased number of osteoclasts, suggesting the alternative NF-\u03baB pathway as a potential drug target for the amelioration of bone disease. In the present study, wild-type (WT) and <jats:italic>aly\/aly<\/jats:italic> mice were subjected to silk ligation to establish a periodontitis model. Alveolar bone resorption was suppressed in <jats:italic>aly\/aly<\/jats:italic> mice by decreased numbers of osteoclasts in the alveolar bone in comparison to WT mice. Furthermore, the expression of receptor activator of NF-\u03baB ligand (RANKL) and TNF\u03b1 (cytokines involved in osteoclast induction in periligative gingival tissue) was decreased. When primary osteoblasts (POBs) and bone marrow cells (BMCs) derived from WT and <jats:italic>aly\/aly<\/jats:italic> mice were prepared and co-cultured, osteoclasts were induced from WT-derived BMCs, regardless of the origin of the POBs, but hardly formed from <jats:italic>aly\/aly<\/jats:italic> 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-\u03baB alternative pathway can be a therapeutic target for periodontal disease.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1179007","type":"journal-article","created":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T05:01:04Z","timestamp":1681794064000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of non-canonical NF-\u03baB signaling suppresses periodontal inflammation and bone 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