Drs. Kwok and Cho contributed equally to this work.
Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis
Article first published online: 28 FEB 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 3, pages 740–751, March 2012
How to Cite
Kwok, S.-K., Cho, M.-L., Park, M.-K., Oh, H.-J., Park, J.-S., Her, Y.-M., Lee, S.-Y., Youn, J., Ju, J. H., Park, K. S., Kim, S.-I., Kim, H.-Y. and Park, S.-H. (2012), Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis. Arthritis & Rheumatism, 64: 740–751. doi: 10.1002/art.33390
- Issue published online: 28 FEB 2012
- Article first published online: 28 FEB 2012
- Accepted manuscript online: 3 OCT 2011 09:30AM EST
- Manuscript Accepted: 11 SEP 2011
- Manuscript Received: 27 SEP 2010
- Basic Science Research Program through the National Research Foundation of Korea
- Ministry of Education, Science and Technology. Grant Number: 20008-2005645
- Korea Health Technology R&D Project
- Ministry for Health, Welfare & Family Affairs, Republic of Korea. Grant Number: A092258
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 4–α-helical bundle type 1 cytokine, has osteoclastogenic activity in patients with RA and in mice with collagen-induced arthritis (CIA).
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.
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.
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.