The Specific Role of Glutaredoxin2 Isoform b (Glrx2b) in RANKL-Induced Osteoclastogenesis Through Activation of the p38-MAPK Signaling Pathway

Chang-Hoon Lee¹, Wan-Hee Yoo², Jin-Jung Choi³, Myong-Joo Hong⁴, Ji-Min Kim⁵ and Jeong-Tae Yeon⁶, ¹Department of Internal Medicine, School of medicine, Wonkwang university, Iksan, Chonbuk, South Korea, ²Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea, ³Internal Medicine, CHA University Hospital, Seongnam, South Korea, ⁴Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea, ⁵Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea, ⁶Department of anatomy, school of medicine, Wonkwang university, Iksan, Chonbuk, South Korea

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: antioxidants and osteoclastogenesis, RANK/RANKL pathway

Session Information

Title: Osteoporosis and Metabolic Bone Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose: 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.

Conclusion: Taken together, these results suggest that Glrx2b enhances RANKL-induced osteoclastogenesis via p38 activation. It may be very useful information for treatment of bone-resorbing disorders, such as rheumatoid arthritis and osteoporosis.

Disclosure:

C. H. Lee,
None;

W. H. Yoo,
None;

J. J. Choi,
None;

M. J. Hong,
None;

J. M. Kim,
None;

J. T. Yeon,
None.

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