Abstract
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.
Highlights
As well as supporting and protecting the body, bones support movement in coordination with muscles, host hematopoiesis, and store minerals such as calcium [1,2]
IKKβ-deficient osteoclasts resulted in RANKL-induced apoptosis by the activation of c-Jun N-terminal kinase (JNK), and the addition of JNK inhibitor restored RANKL-induced apoptosis derived from IKKβcKO mice in vitro [33]
Bone resorption is enhanced in a state of inflammation, and bone mass is reduced when bone formation is inhibited
Summary
As well as supporting and protecting the body, bones support movement in coordination with muscles, host hematopoiesis, and store minerals such as calcium [1,2]. Synovial cells produce inflammatory cytokines, the T-cell immune reaction in the RA synovium causes an excessive biological reaction, and the suchsignal as interleukin (IL)-1, and tumor necrosis (TNF)-α, enzymes, in the synovial cellsIL-6, is continually activated. RelB/p52 is formed and and which has the same function as IκBs, is degraded, and a heterodimer of RelB/p52 is formed translocates into the nucleus This activation pathway is referred to as “the alternative NF-ĸB translocates into the nucleus. (Figure 1) [9,10,11] Since these two pathways play different roles, the p50/p65, p50/c-Rel, and p52/RelB and p52/RelB heterodimers are expected to bind to their specific DNA sequences. We will mainly explain the physiological and pathological roles of NF-κB in bone development and disease, focusing on osteoclasts and osteoblasts
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
