Session Title: Biology and Pathology of Bone and Joint
Session Type: Abstract Submissions (ACR)
Stromal cell-derived factor (SDF)-1 is involved in bone destructive process in rheumatoid arthritis (RA) and bony metastasis in malignancy, through inducing angiogenesis, producing matrix-degrading enzymes and increasing survival and migration of osteoclasts. This study aimed to determine the mechanism of SDF-1 on osteoclastogenesis in RA.
Synovial fibroblasts and CD4+ T cells were isolated from synovial tissues and peripheral blood of RA patients. The expression of SDF-1 and RANKL in the synovial tissues was evaluated using confocal microscopy. After synovial fibroblasts and CD4+ T cells were treated with rhSDF-1, the expression of RANKL mRNA was determined using real-time PCR. Osteoclastogenesis was analyzed in culture of human peripheral blood monocytes with SDF-1. Osteoclastogenesis was also determined after monocytes were co-cultured with rhSDF-1-stimulated RA synovial fibroblasts and CD4+ T cells.
Results: The expression of RANKL mRNA in RA synovial fibroblasts and CD4+ T cells was increased after SDF-1 stimulation. When RA synovial fibroblasts and CD4+ T cells were cultured with neutralizing antibody of TNF-a, the SDF-1-induced RANKL expression decreased, however, inhibition of IL-1b and IL-6 did not affect SDF-1-induced RANKL expression in both cell types. When CD14+ monocytes were cultured with SDF-1 in the absence of exogenous RANKL, the monocytes were differentiated into TRAP+ osteoclasts. Also, the monocytes were differentiated into TRAP+ osteoclasts when they were co-cultured with SDF-1-prestimulated RA synovial fibroblasts or CD4+T cells in the absence of exogenous RANKL.
SDF-1 induced osteoclastogenesis by up-regulating RANKL expression in RA synovial fibroblasts and CD4+T cells and this is mediated by TNF-a. The axis of SDF-1 and RANKL is a potential therapeutic target for bony destructive process in RA.
H. R. Kim,
K. W. Kim,
B. M. Kim,
M. L. Cho,
S. H. Lee,
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/sdf-1-induces-osteoclastogenesis-in-rheumatoid-arthritis-by-upregulating-of-rankl-expression-in-synovial-fibroblasts-and-cd4-t-cells/