title: Glutaredoxin2 isoform b (Glrx2b) promotes RANKL-induced osteoclastogenesis through activation of the p38-MAPK signaling pathway.
abstract: 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 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.
authors.affiliation: Department of Anatomy & Institute for Skeletal Diseases, School of Medicine, Wonkwang University Iksan, Korea.
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Yeon
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Kie-In
authors.initials: KI
authors.lastname: Park
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Choi
authors.forename: Jeong-Joong
authors.initials: JJ
authors.lastname: Kim
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Youn
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054477:Glutaredoxins / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C516009:Glrx2 protein, mouse; D054477:Glutaredoxins; D007527:Isoenzymes; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases