骨溶解
破骨细胞
NF-κB
骨吸收
兰克尔
癌症研究
细胞生物学
NFKB1型
信号转导
炎症
化学
免疫学
医学
生物
激活剂(遗传学)
内科学
受体
转录因子
生物化学
外科
基因
作者
Jiake Xu,Hua Fei Wu,Estabelle S.M. Ang,Kirk H. M. Yip,Magdalene Woloszyn,Minghao Zheng,Ren Xiang Tan
标识
DOI:10.1016/j.cytogfr.2008.11.007
摘要
Osteoclasts are responsible for bone resorption and play a pivotal role in the pathogenesis of osteolytic disorders. NF-kappaB is a set of nuclear factors that bind to consensus DNA sequences called kappaB sites, and is essential for osteoclast formation and survival. NF-kappaB signalling pathways are strictly regulated to maintain bone homeostasis by cytokines such as RANKL, TNF-alpha and IL-1, which differentially regulate classical and/or alternative NF-kappaB pathways in osteoclastic cells. These pathways are also modulated by NF-kappaB mediators, including TRAF6, aPKC, p62/SQSTM1 and deubiquitinating enzyme CYLD that are involved in the ubiquitin-proteasome system during RANK-mediated osteoclastogenesis. Abnormal activation of NF-kappaB signalling in osteoclasts has been associated with excessive osteoclastic activity, and frequently observed in osteolytic conditions, including periprosthetic osteolysis, arthritis, Paget's disease of bone, and periodontitis. NF-kappaB modulators such as parthenolide and NEMO-binding domain peptide demonstrate therapeutic effects on inflammation-induced bone destruction in mouse models. Unravelling the structure and function of NF-kappaB pathways in osteoclasts and other cell types will be important in developing new strategies for treatments of bone diseases.
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