Session 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.
C. H. Lee,
W. H. Yoo,
J. J. Choi,
M. J. Hong,
J. M. Kim,
J. T. Yeon,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-specific-role-of-glutaredoxin2-isoform-b-glrx2b-in-rankl-induced-osteoclastogenesis-through-activation-of-the-p38-mapk-signaling-pathway/