Background Th17 cells, which are defined by a selective interleukin (IL)-17 secretion, are involved in the bony destruction of rheumatoid arthritis (RA).
Objectives This study aimed to determine the regulatory effect of Th17 cytokines on the osteoclastogenesis in 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.
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Disclosure of Interest None declared