1. [NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB].
- Author
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Jimi E and Fukushima H
- Subjects
- Animals, Carcinoma, Squamous Cell pathology, Disease Models, Animal, Humans, Jaw pathology, Jaw Neoplasms pathology, Mice, Neoplasm Invasiveness, RANK Ligand, Benzamides administration & dosage, Benzamides pharmacology, Benzamides therapeutic use, Carcinoma, Squamous Cell drug therapy, Cell Differentiation drug effects, Cell Differentiation genetics, Jaw Neoplasms drug therapy, NF-kappa B antagonists & inhibitors, NF-kappa B physiology, Osteoblasts cytology, Osteoclasts cytology, Osteogenesis drug effects, Osteogenesis genetics, Signal Transduction genetics, Signal Transduction physiology
- Abstract
The transcriptional factor nuclear factor κB(NF-κB)regulates the expression of a wide variety of genes that are involved in immune and inflammatory responses, proliferation, and tumorigenesis. NF-κB consists of five members, such as p65(RelA), RelB, c-Rel, p50/p105(NF-κB1), and p52/p100(NF-κB2). There are two distinct NF-κB activation pathways, termed the classical and alternative NF-κB signaling pathways. Since mice lacking both p50 and p52 subunits developed typical osteopetrosis, due to total lack of osteoclasts, NF-κB is also important osteoclast differentiation. A selective NF-κB inhibitor blocked receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis both in vitro and in vivo. Recent findings have shown that inactivation of NF-κB enhances osteoblast differentiation in vitro and bone formation in vivo. NF-κB is constitutively activated in many cancers including oral squamous cell carcinoma(OSCC), and is involved in the invasive characteristics of OSCC. A selective NF-κB inhibitor also prevented jaw bone destruction by OSCC by reduced osteoclast numbers in animal model. Thus the inhibition of NF-κB might useful for the treatment of bone diseases, such as arthritis, osteoporosis, periodontitis, and bone invasion by OSCC by inhibiting bone resorption and by stimulating bone formation.
- Published
- 2016
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