The Role of NF-κB in Physiological Bone Development and Inflammatory Bone Diseases: Is NF-κB Inhibition "Killing Two Birds with One Stone"?
Nuclear factor-κB (NF-κB) is a transcription factor that regulates the expression of various genes involved in inflammation and the immune response. The activation of NF-κB occurs via two pathways: inflammatory cytokines, such as TNF-α and IL-1β, activate the "classical pathway", and cytokines involved in lymph node formation, such as CD40L, activate the "alternative pathway". NF-κB1 (p50) and NF-κB2 (p52) double-knockout mice exhibited severe osteopetrosis due to the total lack of osteoclasts, suggesting that NF-κB activation is required for osteoclast differentiation. These results indicate that NF-κB 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 IκB kinase (IKK)-β specifically in osteoblasts exhibited increased bone mass, but there was no change in osteoclast numbers. Therefore, inhibition of NF-κB is thought to promote bone formation. Taken together, the inhibition of NF-κB leads to "killing two birds with one stone": it suppresses bone resorption and promotes bone formation. This review describes the role of NF-κB in physiological bone metabolism, pathologic bone destruction, and bone regeneration.
['Jimi|Eijiro|E|0000-0003-3616-5299', 'Takakura|Nana|N|', 'Hiura|Fumitaka|F|', 'Nakamura|Ichiro|I|', 'Hirata-Tsuchiya|Shizu|S|0000-0003-1520-8587']
D000818:Animals D001846:Bone Development D001847:Bone Diseases D001862:Bone Resorption D002454:Cell Differentiation D016207:Cytokines D006801:Humans D020672:I-kappa B Proteins D007249:Inflammation D016328:NF-kappa B D010006:Osteoblasts D010010:Osteoclasts D010012:Osteogenesis D015398:Signal Transduction D014409:Tumor Necrosis Factor-alpha
NF-κB inflammation osteoclasts osteoblasts