We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Reciprocal Activation of CD4+ T Cells and Synovial Fibroblasts by Stromal Cell-Derived Factor 1 Promotes RANKL Expression and Osteoclastogenesis in Rheumatoid Arthritis.
- Authors
Kim, Hae‐Rim; Kim, Kyoung‐Woon; Kim, Bo‐Mi; Jung, Hong‐Geun; Cho, Mi‐La; Lee, Sang‐Heon
- Abstract
Objective Stromal cell-derived factor 1 (SDF-1) is a chemokine that is involved in the bone-destructive process in rheumatoid arthritis (RA) and bony metastasis in malignancy. This study was undertaken to determine the role and mechanism of SDF-1 in RA-associated osteoclastogenesis. Methods The expression of SDF-1, tumor necrosis factor α (TNFα), and RANKL in RA synovial tissue was analyzed using confocal microscopy. After synovial fibroblasts and CD4+ T cells were treated with SDF-1, RANKL messenger RNA expression was determined by real-time and reverse transcription polymerase chain reaction. Osteoclastogenesis was assessed by counting tartrate-resistant acid phosphatase-positive multinucleated cells in CD14+ monocytes cultured with SDF-1 in the presence of anticytokine antibodies or signal inhibitors and in monocytes cocultured with SDF-1-pretreated synovial fibroblasts and CD4+ T cells. Results RANKL, TNFα, and SDF-1 were coexpressed in the lining and sublining of RA synovium. SDF-1 stimulated RANKL expression in RA synovial fibroblasts and CD4+ T cells, and TNFα inhibition reduced this stimulation. When monocytes isolated from human peripheral blood were cultured with SDF-1, they were differentiated into osteoclasts in the absence of RANKL. Monocytes were also differentiated into osteoclasts when they were cocultured with SDF-1-pretreated synovial fibroblasts or CD4+T cells; however, this osteoclastogenesis was reduced by TNFα inhibition. Conclusion Our findings indicate that SDF-1 induces osteoclastogenesis directly and indirectly via up-regulating RANKL expression in RA synovial fibroblasts and CD4+ T cells, and that this is mediated by TNFα. The axis of SDF-1 and RANKL is a potential therapeutic target for RA-associated bone destruction.
- Subjects
SOUTH Korea; FIBROBLASTS; T cells; ACADEMIC medical centers; POLYMERASE chain reaction; RESEARCH funding; RHEUMATOID arthritis; STATISTICS; U-statistics; WESTERN immunoblotting; DATA analysis; REVERSE transcriptase polymerase chain reaction; PHYSIOLOGY
- Publication
Arthritis & Rheumatology, 2014, Vol 66, Issue 3, p538
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.38286