Strength of TRAF6 signalling determines osteoclastogenesis

被引:69
作者
Kadono, Y
Okada, F
Perchonock, C
Jang, HD
Lee, SY
Kim, N
Choi, Y
机构
[1] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[2] Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea
[3] Ewha Womans Univ, Ctr Cell Signaling Res, Seoul 120750, South Korea
[4] Chonnam Natl Univ, Sch Med, Med Res Ctr Gene Regulat, Kwangju 501190, South Korea
关键词
osteoclast; TRAF6; TRANCE; CD40; signal;
D O I
10.1038/sj.embor.7400345
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:171 / 176
页数:6
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