Glutaredoxin2 isoform b (Glrx2b) promotes RANKL-induced osteoclastogenesis through activation of the p38-MAPK signaling pathway

Jeong-Tae Yeon, Sik-Won Choi, Kie-In Park, Min-Kyu Choi, Jeong-Joong Kim, Byung-Soo Youn, Myeung-Su Lee, Jae-Min Oh
2012 BMB Reports  
Receptor activator of NF-κB ligand (RANKL) triggers the differentiation of bone marrow-derived monocyte/macrophage precursor cells (BMMs) of hematopoietic origin into osteoclasts through the activation of mitogen-activated protein (MAP) kinases and transcription factors. Recently, reactive oxygen species (ROS) and antioxidant enzymes were shown to be closely associated with RANKL-mediated osteoclast differentiation. Although glutare-doxin2 (Glrx2) plays a role in cellular redox homeostasis, its
more » ... ox homeostasis, its role in RANKL-mediated osteoclastogenesis is unclear. We found that Glrx2 isoform b (Glrx2b) expression is induced during RANKLmediated osteoclastogenesis. Over-expression of Glrx2b strongly enhanced RANKL-mediated osteoclastogenesis. In addition, Glrx2b-transduced BMMs enhanced the expression of key transcription factors c-Fos and NFATc1, but pre-treatment with SB203580, a p38-specific inhibitor, completely blocked this enhancement. Conversely, down-regulation of Glrx2b decreased RANKL-mediated osteoclastogenesis and the expression of c-Fos and NFATc1 proteins. Also, Glrx2b down-regulation attenuated the RANKL-induced activation of p38. Taken together, these results suggest that Glrx2b enhances RANKL-induced osteoclastogenesis via p38 activation. [BMB reports 2012; 45(3): 171-176] Effect of Glrx2b on osteoclastogenesis Jeong-Tae Yeon, et al.
doi:10.5483/bmbrep.2012.45.3.171 pmid:22449704 fatcat:kgc2hkcvxjaujolojzmjec6ija