title: [NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB].
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.
authors.affiliation: Division of Molecular Signaling and Biochemistry, Department of Health Promotion, Kyushu Dental University, Japan.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Jimi
authors.affiliation: Center for Advanced Stem Cell and Regenerative Research, Tohoku University Graduate School of Dentistry, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Fukushima
mesh_terms: D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D007568:Jaw / Q000473:pathology; D007573:Jaw Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D009361:Neoplasm Invasiveness; D010006:Osteoblasts / Q000166:cytology*; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics*; D053245:RANK Ligand; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*
chemical_list: D001549:Benzamides; C503742:N-(2,5-bis(trifluoromethyl)phenyl)-5-bromo-2-hydroxybenzamide; D016328:NF-kappa B; D053245:RANK Ligand