{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T19:06:07Z","timestamp":1793646367479,"version":"4.5.1"},"reference-count":99,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T00:00:00Z","timestamp":1576281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan","award":["JP17K11706"],"award-info":[{"award-number":["JP17K11706"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nuclear factor-\u03baB (NF-\u03baB) is a transcription factor that regulates the expression of various genes involved in inflammation and the immune response. The activation of NF-\u03baB occurs via two pathways: inflammatory cytokines, such as TNF-\u03b1 and IL-1\u03b2, activate the \u201cclassical pathway\u201d, and cytokines involved in lymph node formation, such as CD40L, activate the \u201calternative pathway\u201d. NF-\u03baB1 (p50) and NF-\u03baB2 (p52) double-knockout mice exhibited severe osteopetrosis due to the total lack of osteoclasts, suggesting that NF-\u03baB activation is required for osteoclast differentiation. These results indicate that NF-\u03baB may be a therapeutic target for inflammatory bone diseases, such as rheumatoid arthritis and periodontal disease. On the other hand, mice that express the dominant negative form of I\u03baB kinase (IKK)-\u03b2 specifically in osteoblasts exhibited increased bone mass, but there was no change in osteoclast numbers. Therefore, inhibition of NF-\u03baB is thought to promote bone formation. Taken together, the inhibition of NF-\u03baB leads to \u201ckilling two birds with one stone\u201d: it suppresses bone resorption and promotes bone formation. This review describes the role of NF-\u03baB in physiological bone metabolism, pathologic bone destruction, and bone regeneration.<\/jats:p>","DOI":"10.3390\/cells8121636","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T05:19:38Z","timestamp":1576473578000},"page":"1636","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":137,"title":["The Role of NF-\u03baB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-\u03baB Inhibition \u201cKilling Two Birds with One Stone\u201d?"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3616-5299","authenticated-orcid":false,"given":"Eijiro","family":"Jimi","sequence":"first","affiliation":[{"name":"Oral Health\/Brain Health\/Total Health Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"},{"name":"Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nana","family":"Takakura","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumitaka","family":"Hiura","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Science, Teikyo Heisei University, 2-51-4 Higashi-Ikebukuro, Toshima, Tokyo 170-8445, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1520-8587","authenticated-orcid":false,"given":"Shizu","family":"Hirata-Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Biological Endodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,14]]},"reference":[{"key":"ref_1","unstructured":"Bilezikian, J.P., Raisz, L.G., and Rodan, G.A. 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