Background Stromal cell-derived factor (SDF)-1 (CXCL12) is a chemokine promoting the migration of inflammatory cells into the inflamed synovium in rheumatoid arthritis (RA). The expression of SDF-1 is elevated in serum, synovial fluid, and synovial tissues and it can promote joint destruction by inducing angiogenesis and MMP production.
Objectives This study aims to determine the effect and mechanism of SDF-1 on bony destructive process in RA through RANKL regulation from synovial fibroblasts and CD4+ T cells.
Methods Synovial fibroblasts were isolated from synovial tissues of RA patients and CD4+ T cells were isolated from PBMC of RA patients. After RA synovial fibroblasts and CD4+ T cells were treated with rhSDF-1, the expression of RANKL mRNA was determined using real-time PCR. After inhibition of pro-inflammatory cytokines or intracellular signal molecules, the change of the SDF-1-induced RANKL expression was analyzed.
Results The expression of RANKL mRNA in RA synovial fibroblasts was increased after SDF-1 stimulation in a dose dependent manner. The expression of RANKL mRNA in RA CD4+ T cells was also increased after SDF-1 stimulation in a similar pattern with synovial fibroblasts. After RA synovial fibroblasts were cultured with neutralizing antibodies of TNF-a and IL-6, the expression of RANKL mRNA was decreased in RA synovial fibroblasts. The expression of RANKL mRNA was decreased after CD4+ T cells were cultured with SDF-1 in presence of IL-1b, TNF-a and IL-6. SDF-1-induced RANKL expression was also diminished after inhibition of PI3 kinase, p38 MAP kinase, and JNK.
Conclusions This result suggests that SDF-1 could induce RANKL from RA synovial fibroblasts mediated by TNF-a and IL-6. In RA CD4+ T cells, SDF-1-induced RANKL expression is mediated by IL-1b as well as TNF-a and IL-6.
Disclosure of Interest None Declared
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