Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis
- Title
- Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis
- Author
- 윤지희
- Keywords
- SYSTEMIC-LUPUS-ERYTHEMATOSUS; NECROSIS-FACTOR-ALPHA; T-CELL-ACTIVATION; BXSB-YAA MICE; RECEPTOR ACTIVATOR; BONE DESTRUCTION; SYNOVIAL FIBROBLASTS; RADIOLOGIC DAMAGE; TH17 CELLS; IL-21
- Issue Date
- 2012-03
- Publisher
- Wiley-Blackwell
- Citation
- Arthritis & Rheumatism, 2012, 64(3), P.740-751
- Abstract
- Objective Bone destruction is a critical pathology involved in the functional disability caused by rheumatoid arthritis (RA). Osteoclasts, which are specialized bone-resorbing cells regulated by cytokines such as RANKL, are implicated in bone destruction in RA. The aim of this study was to determine whether interleukin-21 (IL-21), a potent immunomodulatory 4a-helical bundle type 1 cytokine, has osteoclastogenic activity in patients with RA and in mice with collagen-induced arthritis (CIA). Methods. The expression of IL-21 in synovial tissue was examined using immunohistochemistry. The concentrations of IL-21 in serum and synovial fluid were determined by enzyme-linked immunosorbent assay. The levels of RANKL and osteoclastogenic markers were measured using real-time polymerase chain reaction. CD14+ monocytes from patients with RA or mouse bone marrow cells were cocultured with fibroblast-like synoviocytes (FLS) from patients with RA or CD4+ T cells from mice with CIA in the presence of IL-21 and subsequently stained for tartrate-resistant acid phosphatase activity to determine osteoclast formation. Results. IL-21 was up-regulated in the synovium, synovial fluid, and serum of patients with RA and in the synovium and serum of mice with CIA. IL-21 induced RANKL expression in mixed joint cells and CD4+ T cells from mice with CIA and in CD4+ T cells and FLS from patients with RA. Moreover, IL-21 enhanced in vitro osteoclastogenesis without the presence of RANKL-providing cells and by inducing RANKL expression in CD4+ T cells and FLS. Conclusion. Our data suggest that IL-21 promotes osteoclastogenesis in RA. We believe that therapeutic strategies targeting IL-21 might be effective for the treatment of patients with RA, especially in preventing bone destruction.
- URI
- https://onlinelibrary.wiley.com/doi/abs/10.1002/art.33390https://repository.hanyang.ac.kr/handle/20.500.11754/69552
- ISSN
- 2326-5205
- DOI
- 10.1002/art.33390
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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