title: Osteoclasts in arthritis and Th17 cell development.
abstract: Bone destruction associated with rheumatoid arthritis (RA) is mainly attributed to the abnormal activation of osteoclasts, which are terminally differentiated cells of monocyte/macrophage lineage that resorb bone matrix. Studies on the immune regulation of osteoclasts in RA have promoted the new research field of "osteoimmunology", which investigates the interplay of the skeletal and immune systems at the molecular level. This interdisciplinary field is proving to be crucial to advances in the treatment of diseases associated with the bone and/or immune systems. As for the mechanisms of the bone destruction found in RA, accumulating evidence lends support to the theory that interleukin (IL)-17-producing helper T (Th17) cells induce the expression of receptor activator of nuclear factor-κB ligand (RANKL) in synovial cells, which in turn stimulates the differentiation and activation of osteoclasts together with inflammatory cytokines. Thus, inhibition of Th17 is potentially beneficial for the amelioration of the bone damage which occurs in RA. A recent study revealed that IκBζ is essential to the development of Th17 cells. These findings comprise an important advance in our understanding of the pathogenesis of RA and potentially effective therapeutic strategies.
authors.affiliation: Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Okamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takayanagi
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000503:physiopathology; D001862:Bone Resorption; D002454:Cell Differentiation; D006801:Humans; D007249:Inflammation; D020381:Interleukin-17 / Q000276:immunology*; D010010:Osteoclasts / Q000276:immunology*; D053245:RANK Ligand / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D053245:RANK Ligand