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

• Main Authors: Jeong-Tae Yeon, Sik-Won Choi, Kie-In Park, Min-Kyu Choi, Jeong-Joong Kim, Byung-Soo Youn, Myeung Su Lee, Jaemin Oh
• Format: Article
• Language: English
• Published: Korean Society for Biochemistry and Molecular Biology 2012-03-01
• Series: BMB Reports
• Subjects: Glrx2b; Glutaredoxin2 isoform b; Osteoclasts; p38; RANKL
• Online Access: http://bmbreports.org/jbmb/pdf.php?data=MTMxMTA4MTZAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS0zJTVEMTIwMzI3MTU0Nl8lMjgxNzEtMTc2JTI5Qk1CXzExLTIyNy5wZGY=

Receptor activator of NF-κB ligand (RANKL) triggers thedifferentiation of bone marrow-derived monocyte/macrophageprecursor cells (BMMs) of hematopoietic origin into osteoclaststhrough the activation of mitogen-activated protein (MAP) kinasesand transcription factors. Recently, reactive oxygen species (ROS)and antioxidant enzymes were shown to be closely associated withRANKL-mediated osteoclast differentiation. Although glutaredoxin2(Glrx2) plays a role in cellular redox homeostasis, its role inRANKL-mediated osteoclastogenesis is unclear. We found thatGlrx2 isoform b (Glrx2b) expression is induced during RANKLmediatedosteoclastogenesis. Over-expression of Glrx2b stronglyenhanced RANKL- mediated osteoclastogenesis. In addition,Glrx2b-transduced BMMs enhanced the expression of key transcriptionfactors c-Fos and NFATc1, but pre-treatment withSB203580, a p38-specific inhibitor, completely blocked thisenhancement. Conversely, down-regulation of Glrx2b decreasedRANKL- mediated osteoclastogenesis and the expression of c-Fosand NFATc1 proteins. Also, Glrx2b down-regulation attenuated theRANKL-induced activation of p38. Taken together, these resultssuggest that Glrx2b enhances RANKL-induced osteoclastogenesisvia p38 activation. [BMB reports 2012; 45(3): 171-176]