FRI0392 The specific role of glutaredoxin2 isoform B (GLRX2B) in rankl-induced osteoclastogenesis through activation of the P38-MAPK signaling pathway. (23rd January 2014)

• Record Type: Journal Article
• Authors: Lee, M.-S.; Yeon, J.-T.; Oh, J.-M.; Choi, J.-U.; Yoo, W.-H.
• Is Part Of: Annals of the rheumatic diseases. Volume 71(2012)Supplement 3
• Page Start: 447
• Page End: 447
• Publication Date: 2014-01-23
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2012-eular.2849
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: 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. Objectives: The aim of this study was to examine the effect of Glrx2 on osteoclast differentiation Methods: Osteoclast formation was evaluated in bone marrow cells (BMC) in specific condition with over-expression of Glrx2 or down- regulation of Glrx2 during receptor activator of NF-κB ligand (RANKL)- mediated osteoclastogenesis. The expression of c-fos and NFATc1 mRNA in osteoclast precursor were assessed by RT-PCR. The levels of c-fos and NFATc1 protein were assessed by western blot. Also the mitogen-activated protein (MAPK)s pathways were measured using Western blot analysis. Results: We found that Glrx2 isoform b (Glrx2b) expression is induced during RANKL-mediated 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. Conclusions: Taken together, these results suggest that Glrx2b enhances RANKL-induced osteoclastogenesis via p38 activation. It may bevery useful information for treatment of bone-resorbing disorders, such as rheumatoid arthritis and osteoporosis. Disclosure of Interest: None Declared