title: The interaction of monocytes with rheumatoid synovial cells is a key step in LIGHT-mediated inflammatory bone destruction.
abstract: Formation of osteoclasts and consequent joint destruction are hallmarks of rheumatoid arthritis (RA). Here we show that LIGHT, a member of the tumour necrosis factor (TNF) superfamily, induced the differentiation into tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells (MNCs) of CD14(+) monocytes cocultured with nurse-like cells isolated from RA synovium, but not of freshly isolated CD14(+) monocytes. Receptor activator of nuclear factor-kappaB ligand (RANKL) enhanced this LIGHT-induced generation of TRAP-positive MNCs. The MNCs showed the phenotypical and functional characteristics of osteoclasts; they showed the expression of osteoclast markers such as cathepsin K, actin-ring formation, and the ability to resorb bone. Moreover, the MNCs expressed both matrix metalloproteinase 9 (MMP-9) and MMP-12, but the latter was not expressed in osteoclasts induced from CD14(+) monocytes by RANKL. Immunohistochemical analysis showed that the MMP-12-producing MNCs were present in the erosive areas of joints in RA, but not in the affected joints of osteoarthritic patients. These findings suggested that LIGHT might be involved in the progression of inflammatory bone destruction in RA, and that osteoclast progenitors might become competent for LIGHT-mediated osteoclastogenesis via interactions with synoviocyte-like nurse-like cells.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan. satoru.ishida@shionogi.co.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishida
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamane
authors.forename: Saori
authors.initials: S
authors.lastname: Nakano
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagimoto
authors.forename: Yukie
authors.initials: Y
authors.lastname: Hanamoto
authors.forename: Miki
authors.initials: M
authors.lastname: Maeda-Tanimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyosaki-Maeda
authors.forename: Jun
authors.initials: J
authors.lastname: Ishizaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsuo
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
authors.forename: Tsunetoshi
authors.initials: T
authors.lastname: Itoh
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochi
authors.forename: Ryuji
authors.initials: R
authors.lastname: Suzuki
mesh_terms: D000135:Acid Phosphatase / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001862:Bone Resorption / Q000276:immunology / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D056657:Cathepsin K / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000494:pharmacology / Q000502:physiology*
chemical_list: D007527:Isoenzymes; D053245:RANK Ligand; C505688:TNFSF11 protein, human; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; C534130:CTSK protein, human; D056657:Cathepsin K; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12