| First Author | Yamaguchi N | Year | 2012 |
| Journal | Genes Cells | Volume | 17 |
| Issue | 12 | Pages | 971-81 |
| PubMed ID | 23126497 | Mgi Jnum | J:214051 |
| Mgi Id | MGI:5587906 | Doi | 10.1111/gtc.12012 |
| Citation | Yamaguchi N, et al. (2012) cIAP1/2 negatively regulate RANKL-induced osteoclastogenesis through the inhibition of NFATc1 expression. Genes Cells 17(12):971-81 |
| abstractText | Receptor activator of nuclear factor kappaB (RANK) is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and triggers osteoclastogenesis by inducing the expression of NFATc1 through the activation of the NF-kappaB and MAPK pathways. Cellular inhibitors of apoptosis proteins 1 and 2 (cIAP1/2), which are ubiquitin E3 ligases, are involved in the activation of the NF-kappaB and MAPK pathways by various members of the TNFRSF. However, the involvement of cIAP1/2 in RANK signaling has remained largely unknown. In this study, we reveal the involvement of cIAP1/2 in RANK ligand (RANKL)-induced osteoclastogenesis. The over-expression of cIAP1 or cIAP2 in the mouse monocytic cell line Raw264.7 resulted in the significant suppression of RANKL-induced NFATc1 mRNA expression and osteoclastogenesis, whereas the activation of the NF-kappaB and MAPK pathways was barely changed by these over-expressions. The depletion of endogenous cIAP1/2 by their specific inhibitor MV1 or their siRNA-mediated knockdown resulted in enhanced RANKL-induced NFATc1 expression and osteoclastogenesis without affecting the activation of the NF-kappaB and MAPK pathways. In combination, these results indicate that cIAP1/2 negatively regulate osteoclastogenesis by inhibiting NFATc1 mRNA expression in a manner that is distinct from the previously identified functions of cIAP1/2. |
