2003
DOI: 10.4049/jimmunol.171.10.5547
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Direct Inhibition of NF-κB Blocks Bone Erosion Associated with Inflammatory Arthritis

Abstract: Inflammatory arthritis is associated with devastating joint tissue destruction and periarticular bone erosion. Although secreted products of infiltrating immune cells perpetuate the inflammatory response, the osteolytic component of this disease is a direct result of localized recruitment and activation of osteoclasts. Given that NF-κB plays a central role in both processes, the function of this transcription factor was examined. Using a mouse model of autoreactive Ig transfer that engenders inflammatory arthr… Show more

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Cited by 89 publications
(75 citation statements)
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“…The first proof that blocking NF-kB could potentially be therapeutically efficacious was obtained after the administration of a DN IkB in a mouse model of inflammatory arthritis. 65 In this model, transdominant IkBa was able to block NF-kB activation in arthritic cells, and significantly attenuated osteoclast recruitment and bone erosion. Later on, two different groups successfully inhibited NF-kB activation by blocking IKK activity using a cell-permeable NBD peptide.…”
Section: Nf-jb In Arthritismentioning
confidence: 80%
“…The first proof that blocking NF-kB could potentially be therapeutically efficacious was obtained after the administration of a DN IkB in a mouse model of inflammatory arthritis. 65 In this model, transdominant IkBa was able to block NF-kB activation in arthritic cells, and significantly attenuated osteoclast recruitment and bone erosion. Later on, two different groups successfully inhibited NF-kB activation by blocking IKK activity using a cell-permeable NBD peptide.…”
Section: Nf-jb In Arthritismentioning
confidence: 80%
“…Recent evidence also suggests that NF-B is involved in the bone destruction observed in inflammatory arthritis (41). In addition to its role in inflammation, NF-B contributes to the regulation of immune responses, cell proliferation, and apoptosis.…”
Section: Discussionmentioning
confidence: 99%
“…Direct inhibition of NF-B by mutated I B proteins was shown to be sufficient to block generalized symptoms of the inflammatory arthritis and to specifically arrest both bone erosion and inflammatory arthritis in a mouse model (45). The promoter region of MMP-9 possesses several functional enhancer element-binding sites, such as NF-B and AP-1 sites.…”
Section: Discussionmentioning
confidence: 99%