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FRI0392 The specific role of glutaredoxin2 isoform B (GLRX2B) in rankl-induced osteoclastogenesis through activation of the P38-MAPK signaling pathway
  1. M.-S. Lee1,
  2. J.-T. Yeon2,
  3. J.-M. Oh2,
  4. J.-U. Choi3,
  5. W.-H. Yoo4
  1. 1Devision of Rheumatology, Department of Internal Medicine, Wonkwang University Hospital
  2. 2School of Medicine, Wonkwang University, Iksan
  3. 3Devision of Rheumatology, Department of Internal Medicine, Cha University Hospital, Sugnam
  4. 4Devision of Rheumatology, Department of Internal Medicine, Jeonbuk national university Hospital, Jeonju, Korea, Republic Of

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

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