Article Text

PDF
SAT0016 TH17 Cytokines Regulate Osteoclastogenesis in Rheumatoid Arthritis
  1. H.-R. Kim1,
  2. S.-H. Lee1,
  3. H.-Y. Kim1,
  4. S.-H. Lee2
  1. 1Konkuk University School of Medicine
  2. 2Kyung Hee University School of Medicine, SEOUL, Korea, Republic Of

Abstract

Background Th17 cells, which are defined by a selective interleukin (IL)-17 secretion, are considered as a distinct lineage of CD4+ helper T cells which are regulated by the other Th1 and Th2 cytokines. IL-17A is a dominant proinflammatory cytokine produced by the Th17 cells. IL-21, IL-22 and IL-26 are also produced by the Th17 cells. In RA, IL-17A induces the production of proinflammatory mediators, such as IL-1 and tumor necrosis factor (TNF)-a from synovial fibroblasts, macrophages, and chondrocytes.

Objectives This study aimed to determine the regulatory effect of Th17 cytokines on the osteoclastogenesis in rheumatoid arthritis (RA).

Methods The expression of IL-17 and RANKL was determined in synovial tissue, fibroblast-like synoviocytes (FLS) and synovial fluids of RA patients using immonohistochemical staining, ELISA and real-time PCR. The Th17 cytokines-induced RANKL expression was studied in RA FLS using real-time PCR, luciferase activity, and western blot. Human peripheral blood monocytes were cultured with M-CSF and Th17 cytokines, and then osteoclastogenesis was determined by counting the number TRAP-positive multinucleated cells. The osteoclastogenesis was also determined 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. After RA FLS were stimulated with IL-17, IL-21 and IL-22, the expression of RANKL mRNA increased and the IL-17-induced RANKL expression was decreased by the inhibition of Act1, TRAF6, NF-κB and the AP-1. Th17 cytokines and IL-17-prestimulated FLS induced osteoclastogenesis from monocytes in the absence of osteoblasts or RANKL.

Conclusions Th17 cytokines have a dual effect on osteooclastogenesis in RA; direct induction of osteoclastogenesis from monocytes and upregulation of RANKL production in RA FLS. Th17 cytokines/RANKL axis could be a potential therapeutic target for bone destruction in RA.

Disclosure of Interest None declared

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.