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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Glutaredoxin2 isoform b (Glrx2b) promotes RANKL-induced osteoclastogenesis through activation of the p38-MAPK signaling pathway

  • Yeon, Jeong-Tae (Department of Anatomy & Institute for Skeletal Diseases, School of Medicine, Wonkwang University) ;
  • Choi, Sik-Won (Department of Anatomy & Institute for Skeletal Diseases, School of Medicine, Wonkwang University) ;
  • Park, Kie-In (Division of Biological Sciences, College of Natural Science, Chonbuk National University) ;
  • Choi, Min-Kyu (Department of Anatomy & Institute for Skeletal Diseases, School of Medicine, Wonkwang University) ;
  • Kim, Jeong-Joong (Department of Anatomy & Institute for Skeletal Diseases, School of Medicine, Wonkwang University) ;
  • Youn, Byung-Soo (AdipoGen, Inc.) ;
  • Lee, Myeung-Su (Department of Internal Medicine, Division of Rheumatology and Institute of Wonkwang Medical Science, Wonkwang University) ;
  • Oh, Jae-Min (Department of Anatomy & Institute for Skeletal Diseases, School of Medicine, Wonkwang University)
  • Received : 2011.10.19
  • Accepted : 2011.12.05
  • Published : 2012.03.31
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Abstract

Receptor activator of NF-${\kappa}B$ 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 glutaredoxin2 (Glrx2) plays a role in cellular redox 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.

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References

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