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Strength of TRAF6 signalling determines osteoclastogenesis
Author(s) -
Kadono Yuho,
Okada Fumihiko,
Perchonock Claire,
Jang Hyun Duk,
Lee Soo Young,
Kim Nacksung,
Choi Yongwon
Publication year - 2005
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400345
Subject(s) - receptor , stimulation , trance , microbiology and biotechnology , chemistry , signalling , cd40 , neuroscience , biology , in vitro , biochemistry , philosophy , theology , cytotoxic t cell
TRANCE/TRAF6 signalling governs osteoclastogenesis in vivo . Only the TRANCE receptor (TRANCE‐R) has been shown to induce osteoclastogenesis, even though other immune receptors, including CD40 and IL‐1R/Toll‐like receptor, use TRAF6 to activate overlapping signalling cascades. These observations led us to question whether qualitative or quantitative differences exist between the TRAF6‐mediated signals induced by TRANCE and by other ligand–receptor pairs. Here we show that stimulation by overexpressed wild‐type CD40 can induce osteoclastogenesis. Stimulation through modified CD40 containing increased numbers of TRAF6‐binding sites in the cytoplasmic tails showed a dose‐dependent increase in the activation of p38 kinase and more pronounced osteoclastogenesis. Moreover, precursors overexpressing TRAF6 differentiate into osteoclasts in the absence of additional signals from TRANCE. Our results suggest that differences in the osteoclastogenesis‐inducing capacity of TRANCE‐R versus other TRAF6‐associated receptors may in part stem from a quantitative difference in the TRAF6‐mediated signals.