Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: This study aimed to determine the regulatory effect of Th17 cytokines on osteoclastogenesis in rheumatoid arthritis (RA).
Methods: The expression of interleukin (IL)-17 and receptor activator of nuclear factor kappa-B ligand (RANKL) was determined in synovial tissue, fibroblast-like synoviocytes (FLS), and synovial fluids of RA patients using immunohistochemical staining, ELISA and real-time PCR. Th17 cytokines-induced RANKL expression was studied in RA FLS by using real-time PCR, luciferase activity assays, and western blot. Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and Th17 cytokines, following which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells. Osteoclastogenesis was also evaluated after human monocytes were co-cultured with IL-17-prestimulated FLS.
Results: There was significant correlation between RANKL and IL-17 levels in RA synovial fluid. IL-17, IL-21, and IL-22 increased the expression of RANKL mRNA in RA FLS and the IL-17-induced RANKL expression decreased by the inhibition of Act1, TRAF6, NF-κB and AP-1. Th17 cytokines and IL-17-prestimulated FLS induced osteoclastogenesis from monocytes in the absence of exogenous RANKL. The osteoclastic effect was reduced by inhibition of TNF-a.
Conclusion: Th17 cytokines have a dual effect on osteoclastogenesis in RA: direct induction of osteoclastogenesis from monocytes and upregulation of RANKL production in RA FLS. This Th17 cytokine/RANKL axis could be a potential therapeutic target for bone destruction in RA.
To cite this abstract in AMA style:JUNG MY, Kim HR, KIM HS, KIM HY, Lee SH. Th17 Cytokines Regulate Osteoclastogenesis in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/th17-cytokines-regulate-osteoclastogenesis-in-rheumatoid-arthritis/. Accessed January 17, 2021.
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