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.
journal_name
Immunologyjournal_title
Immunologyauthors
Ishida S,Yamane S,Nakano S,Yanagimoto T,Hanamoto Y,Maeda-Tanimura M,Toyosaki-Maeda T,Ishizaki J,Matsuo Y,Fukui N,Itoh T,Ochi T,Suzuki Rdoi
10.1111/j.1365-2567.2008.02965.xsubject
Has Abstractpub_date
2009-09-01 00:00:00pages
e315-24issue
1 Suppleissn
0019-2805issn
1365-2567pii
IMM2965journal_volume
128pub_type
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