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c IAP 1/2 negatively regulate RANKL ‐induced osteoclastogenesis through the inhibition of NFAT c1 expression
Author(s) -
Yamaguchi Noritaka,
Yokota Mami,
Taguchi Yuu,
Gohda Jin,
Inoue Junichiro
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12012
Subject(s) - rankl , mapk/erk pathway , biology , microbiology and biotechnology , nfat , rank ligand , gene knockdown , signal transduction , nf κb , activator (genetics) , transcription factor , receptor , apoptosis , biochemistry , gene
Receptor activator of nuclear factor κ B ( RANK ) is a member of the tumor necrosis factor receptor superfamily ( TNFRSF ) and triggers osteoclastogenesis by inducing the expression of NFAT c1 through the activation of the NF ‐κ B and MAPK pathways. Cellular inhibitors of apoptosis proteins 1 and 2 ( cIAP 1/2), which are ubiquitin E 3 ligases, are involved in the activation of the NF ‐κ B and MAPK pathways by various members of the TNFRSF . However, the involvement of cIAP 1/2 in RANK signaling has remained largely unknown. In this study, we reveal the involvement of cIAP 1/2 in RANK ligand ( RANKL )‐induced osteoclastogenesis. The over‐expression of c IAP 1 or c IAP 2 in the mouse monocytic cell line R aw264.7 resulted in the significant suppression of RANKL ‐induced NFAT c1 m RNA expression and osteoclastogenesis, whereas the activation of the NF ‐κ B and MAPK pathways was barely changed by these over‐expressions. The depletion of endogenous c IAP 1/2 by their specific inhibitor MV 1 or their si RNA ‐mediated knockdown resulted in enhanced RANKL ‐induced NFAT c1 expression and osteoclastogenesis without affecting the activation of the NF ‐κ B and MAPK pathways. In combination, these results indicate that c IAP 1/2 negatively regulate osteoclastogenesis by inhibiting NFAT c1 mRNA expression in a manner that is distinct from the previously identified functions of c IAP 1/2.