| First Author | Aoki T | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1179007 | PubMed ID | 37143646 |
| Mgi Jnum | J:345984 | Mgi Id | MGI:7470082 |
| Doi | 10.3389/fimmu.2023.1179007 | Citation | Aoki T, et al. (2023) Inhibition of non-canonical NF-kappaB signaling suppresses periodontal inflammation and bone loss. Front Immunol 14:1179007 |
| abstractText | 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-kappaB pathway, exhibited mild osteopetrosis due to decreased number of osteoclasts, suggesting the alternative NF-kappaB 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-kappaB ligand (RANKL) and TNFalpha (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-kappaB alternative pathway can be a therapeutic target for periodontal disease. |
